Cancer Immunotherapy Research Papers - Academia.edu (original) (raw)

2025, Small (Weinheim an der Bergstrasse, Germany)

Gold nanoparticles (AuNPs) are promising vehicles for cancer immunotherapy, with demonstrated efficacy in immune delivery and innate cell stimulation. Nevertheless, their potential has yet to be assessed in the in vivo application of peptide cancer vaccines. In this study, it is hypothesized that the immune distribution and adjuvant qualities of AuNPs could be leveraged to facilitate delivery of the ovalbumin (OVA) peptide antigen and the CpG adjuvant and enhance their therapeutic effect in a B16-OVA tumor model. AuNP delivery of OVA (AuNP-OVA) and of CpG (AuNP-CpG) enhanced the efficacy of both agents and induced strong antigen-specific responses. In addition, it is found that AuNP-OVA delivery alone, without CpG, is sufficient to promote significant antigen-specific responses, leading to subsequent anti-tumor activity and prolonged survival in both prophylactic and therapeutic in vivo tumor models. This enhanced therapeutic efficacy is likely due to the adjuvant effect of peptide ...

2025, Clinical Lymphoma Myeloma and Leukemia

dependent caspase-3 activation, and apoptotic cell death in cells exposed to the compounds. In vivo dose-dependent anti-tumor activity of 747 and 777 has been shown in both mouse models of ALL and AML. In addition, biomarker development and the mechansim of cancer cell selectivity with these compunds will be discussed. In all studies, MSK-777 was found to be at least a log more efficacious and therefore was chosen as the lead candidate to continue preclinical and clinical development. Conclusions: Cdc7 kinase inhibition is a novel and efficacious mode of therapy for the hematologic malignancies. MSK-777 is expected to enter Phase I clinical trials in early 2014.

2025, Nature

Small, soluble metabolites not only are essential intermediates in intracellular biochemical processes, but can also influence neighbouring cells when released into the extracellular milieu 1-3 . Here we identify the metabolite and neurotransmitter GABA as a candidate signalling molecule synthesized and secreted by activated B cells and plasma cells. We show that B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages that secrete interleukin-10 and inhibit CD8 + T cell killer function. In mice, B cell deficiency or B cell-specific inactivation of the GABA-generating enzyme GAD67 enhances anti-tumour responses. Our study reveals that, in addition to cytokines and membrane proteins, small metabolites derived from B-lineage cells have immunoregulatory functions, which may be pharmaceutical targets allowing fine-tuning of immune responses. Lymphocytes are regulated v a variety of receptor interactions with soluble and cell-bound proteins. However, small metabolites derived from immune cells are also abundant in certain tissues, and many may have signalling potential that has yet to be understood. A growing body of research addresses the flux in metabolic products produced and consumed by different immune cells in various stages of differentiation and activation 1-3 . We hypothesized that water-soluble metabolites can serve as environmental cues, and mediate interactions between immune cells. Contrasting homeostatic (non-draining, contralateral; cLN) and activated (draining, ipsilateral; iLN) lymph nodes (LNs) were generated from mice using classic foot-pad immunization with ovalbumin (OVA) protein emulsified in complete Freud's adjuvant (CFA), and subjected to non-targeted profiling of water-soluble metabolites (Fig. ). Principal-component analysis revealed that a strong metabolic shift separated iLNs from cLNs in wild-type (WT) mice (Fig. ). Pathway analysis of around 200 metabolites with significantly different abundance between iLNs and cLNs revealed that the alanine, aspartate and glutamate pathway was the strongest metabolic feature differentiating resting and activated immune sites (Fig. ). Purine and pyrimidine metabolism and the tricarboxylic acid (TCA) cycle were also strongly associated with immune activation (Fig. and Extended Data Fig. ). We assessed the contribution of the main lymphocyte lineages to the metabolic landscape by performing metabolome analyses on activated and resting LNs from immunodeficient mice lacking T cells (Cd3e -/-), B cells (Ighm -/-; referred to hereafter as muMt -/-) or all mature T and B cells (Rag1 -/-). Despite the presence of many pathogen-associated molecules in CFA expected to stimulate pattern recognition receptors on myeloid cell subsets, the iLN profile of Rag1 -/-mice was similar to that of cLNs, suggesting that lymphocyte activation is the dominant factor contributing to the metabolic shift in this acute inflammatory model (Fig. and Extended Data Fig. ). B cells strongly influenced the immunized LN metabolic landscape, as muMt -/-samples were distinct from their WT and Cd3e -/-counterparts (Fig. ). The neurotransmitter GABA (γ-aminobutyric acid), not previously known to be synthesized by B cells, was identified as the major metabolite upregulated in iLNs in a B cell-dependent manner with respect to both fold change and P value (Fig. ). GABA was also detected in resting cLNs from WT and Cd3e -/-mice, at lower levels (Fig. ). However, very little GABA could be detected in LNs from either B cell-deficient mice (muMt -/-) or Rag1 -/-mice, indicating that GABA is a signature B cell metabolite, which was confirmed in random forest algorithm analyses (Fig. and

2025, Research Square (Research Square)

Background: It is well known that tumor-associated macrophages (TAMs) play essential roles in brain tumor resistance to chemotherapy. However, the detailed mechanisms of how TAMs are involved in brain tumor resistance are still unclear and lack a suitable analysis model. Methods: A BV2 microglial cells with ALTS1C1 astrocytoma cells in vitro co-culture system was used to mimic the microglia dominating tumor stroma in the tumor invasion microenvironment and explore the interaction between microglia and brain tumor cells. Results: Our result suggested that microglia could form colonies with glioma cells under high-density culturing conditions and protect glioma cells from apoptosis induced by chemotherapeutic drugs. Moreover, this study demonstrates that microglia could hijack drug substances from the glioma cells and reduce the drug intensity of ALTS1C1 via direct contact. Inhibition of gap junction protein prevented microglial-glioma colony formation and microglia-mediated chemoresistance. Conclusions: This study provides novel insights into how glioma cells acquire chemoresistance via microglia-mediated drug substance transferring, providing a new option for treating chemo-resistant brain tumors.

2025, Frontiers in Immunology

Survivin is overexpressed in various types of human cancer, but rarely expressed in terminally differentiated adult tissues. Thus, survivin is a potential target antigen for a cancer vaccine. However, self-tumor-associated antigens are not highly immunogenic. Bacteria-derived lipoproteins can activate antigen-presenting cells through their tolllike receptors to enhance immune responses. In this context, lipidated survivin is an attractive candidate for cancer immunotherapy. In the present study, recombinant lipidated human survivin (LSur) was prepared from an Escherichia coli-based system. We investigated whether LSur is efficiently captured by antigen-presenting cells then facilitating effective induction of survivin cross-presentation and generation of immunity against cancer cells. Our results demonstrate that LSur, but not its non-lipidated counterpart, can activate mouse bone-marrow-derived-dendritic cells (BMDCs) to enhance cytokine (IL-6, TNF-α, and IL-12) secretion and costimulatory molecules (CD40, CD80, CD86, and MHC II) expression. However, the pathways involved in the capture of the recombinant lipidated antigen by antigen-presenting cells have not yet been elucidated. To this end, we employ various endocytosis inhibitors to study the effect on LSur internalization. We show that the internalization of LSur is suppressed by the inhibition of various routes of endocytosis. These results suggest that endocytosis of LSur by BMDCs can be mediated by multiple mechanisms. Furthermore, LSur is trafficked to the early endosome after internalization by BMDCs. These features of LSur are advantageous for cross-presentation and the induction of antitumor immunity. We demonstrate that immunization of C57BL/6 mice with LSur under treatment with exogenous adjuvant-free formulation induce survivin-specific CD8 + T-cell responses and suppress tumor growth. The antitumor responses are mediated by CD8 + cells. Our findings indicate that LSur is a potential candidate for stimulating protective antitumor immunity. This study suggests that lipidated tumor antigens may be a promising approach for raising a robust antitumor response in cancer immunotherapy.

2025, Frontiers in Oncology

2025, Journal for ImmunoTherapy of Cancer

2025, European Journal of Cancer

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2025, Frontiers in Immunology

Therapeutic monoclonal antibodies targeting immune checkpoints (ICPs) have changed the treatment landscape of many tumors. However, response rate remains relatively low in most cases. A major factor involved in initial resistance to ICP inhibitors is the lack or paucity of tumor T cell infiltration, characterizing the so-called "cold tumors." In this review, we describe the main mechanisms involved in the absence of T cell infiltration, including lack of tumor antigens, defect in antigen presentation, absence of T cell activation and deficit of homing into the tumor bed. We discuss then the different therapeutic approaches that could turn cold into hot tumors. In this way, specific therapies are proposed according to their mechanism of action. In addition, ''supra-physiological'' therapies, such as T cell recruiting bispecific antibodies and Chimeric Antigen Receptor (CAR) T cells, may be active regardless of the mechanism involved, especially in MHC class I negative tumors. The determination of the main factors implicated in the lack of preexisting tumor T cell infiltration is crucial for the development of adapted algorithms of treatments for cold tumors.

2025, Science Advances

Human endogenous retroviruses (HERVs) represent 8% of the human genome. HERV products may represent tumor antigens relevant for cancer immunotherapy. We developed a bioinformatic approach to identify shared CD8 + T cell epitopes derived from cancer-associated HERVs in solid tumors. Six candidates among the most commonly shared HLA-A2 epitopes with evidence of translation were selected for immunological evaluation. In vitro priming assays confirmed the immunogenicity of these epitopes, which induced high-avidity CD8 + T cell clones. These T cells specifically recognize and kill HLA-A2 + tumor cells presenting HERV epitopes on HLA molecules, as demonstrated by mass spectrometry. Furthermore, epitope-specific CD8 + T cells were identified by dextramer staining among tumor-infiltrating lymphocytes from HLA-A2 + patients with breast cancer. Last, we showed that HERV-specific T cells lyse patient-derived organoids. These shared virus-like epitopes are of major interest for the development...

2025, Science Advances

2025

Background: Metastasis in tumor draining lymph nodes (TDLNs) is correlated with poor prognosis in breast cancers. It is associated with local immune suppression, which can be partly due to the higher expression of check point inhibitors in immune cells. The morphological manifestation of the underlying immunomodulation of TDLNs has been less investigated. Here, we present the histomorphological changes and PD1 expression pattern in metastatic and non-metastatic TDLNs in breast cancer patients. Methods: A total of 248 metastatic or non-metastatic TDLNs from 50 breast carcinoma samples were examined histologically and for PD1 expression in the present study. We assessed the immune response in these TDLNs as per histomorphological patterns on H&E stained slides, categorizing them into lymphocyte predominance, germinal center predominance and an un-stimulated pattern. Anti-PD1 immunohistochemistry was performed on all lymph nodes. The results were analyzed using SPSS version 23 and P va...

2025, International Journal of Advanced Multidisciplinary Research and Studies

Background: Neuroblastoma, a common pediatric malignancy, exhibits diverse clinical behavior, necessitating evolving management strategies. This review examines historical milestones, current risk-adapted protocols, and emerging therapies, with insights for resource-limited settings like India. Methods: A systematic search (1950-March 2025) across PubMed, EMBASE, and Cochrane Library identified 40 studies (15 trials, 20 cohorts, 5 reviews) on pediatric neuroblastoma management. Data on interventions, survival, and complications were extracted, with quality assessed using standardized tools. Narrative synthesis was conducted per PRISMA guidelines. Results: Early surgical approaches yielded poor outcomes, but chemotherapy (1960s), MYCN amplification discovery (1985), and INRG risk stratification (2009) improved survival. Low-risk cases achieve >90% overall survival (OS) with surgery, intermediate-risk 94-96% OS with chemotherapy, and high-risk cases approach 50% OS with multimodal therapy, including tandem ASCT and immunotherapy. Emerging therapies (ALK inhibitors, MIBG, CAR T-cells) show promise but face access barriers in India. Conclusion: Neuroblastoma management has advanced significantly, but challenges like relapse, late effects, and resource disparities persist, particularly in India. Precision medicine and localized strategies are critical for future progress.

2025

VG21306 is a novel oncolytic virus (OV) that encodes a secretable bispecific T-cell engager targeting Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6)-expressing tumors. Delivering a T-cell engager locally to a tumor mass will circumvent physical barriers that prevent antibodies from penetrating the tumor, and will mitigate the off-tumor, on-target toxicity risk. Both in vitro and in vivo testing demonstrated the expression of a functional T-cell engager capable of binding both targets. The efficacy of the engager was demonstrated in vitro, where addition of the engager payload to the OV enhanced anti-tumor efficacy against tumor cells overexpressing CEACAM6. Moreover, we have demonstrated the engager’s ability to induce bystander killing in cells lacking CEACAM6 expression, as well as engaging exhausted T cells and inducing tumor cell death. The safety of the engager was demonstrated by the lack of binding to normal human tissue or normal tissue adjacent to tumors, as we...

2025, Biomedical Papers of the Faculty of Medicine of Palacký University, Olomouc Czech Republic

Background. Hyperprogressive disease (HPD) is a new phenomenon that has emerged in the immunotherapy era. HPD is defined as a rapid tumour growth with detrimental effect on the patient condition and disease course. The management and treatment following HPD is not defined. We present here the case report of patient with HPD and review of the literature on putative mechanisms of HPD and following disease management. Methods and Results. A 60-year old male patient with metastatic melanoma was indicated for systemic treatment with anti-programmed cell death (PD)-1 antibody. Rapid tumour growth and detrimental effect on the patient general condition after administration of a single dose of anti-PD-1 antibody met the criteria of HPD. The patient underwent the second line taxane-based chemotherapy with good tolerance and disease stabilization. The third line treatment with anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody ipilimumab was well tolerated and resulted in partial response. Re-challenge with anti-CTLA-4 antibody was feasible, but only with a modest clinical effect. Conclusion. Prompt recognition of HPD and administration of salvage chemotherapy with taxane-based regimens may be crucial. HPD is rarely observed with ipilimumab treatment. Administration of ipilimumab as well as an ipilimumab re-challenge are feasible after HPD on anti-PD-1 antibodies. Investigation of new predictive biomarkers of HPD is warranted as well as new agents that potentiate the immune response in patients affected with this insidious complication.

2025, Cancers

Recently, considerable progress has been achieved in cancer immunotherapy. Targeted immune checkpoint therapies have been established for several forms of cancers, which resulted in a tremendous positive impact on patient survival, even in more advanced tumor stages. With a better understanding of cellular responses to immune checkpoint therapies, it will soon be feasible to find targeted compounds which will make personalized medicine practicable. This is a great opportunity, but it also sets tremendous challenges on both the scientific and clinical aspects. Head and neck tumors evade immune surveillance through various mechanisms. They contain fewer lymphocytes (natural killer cells) than normal tissue with an accumulation of immunosuppressive regulatory T cells. Standard therapies for HNSCC, such as surgery, radiation, and chemotherapy, are becoming more advantageous by targeting immune checkpoints and employing combination therapies. The purpose of this review is to provide an o...

2025, Journal for ImmunoTherapy of Cancer

2025

Therapeutic antibodies targeting immune checkpoints have shown limited efficacy in clinical trials in glioblastoma (GBM) patients. Ultrasound-mediated blood-brain barrier opening (UMBO) using low-intensity pulsed ultrasound improved drug delivery to the brain. We explored the safety and the efficacy of UMBO plus immune checkpoint inhibitors in preclinical models of GBM. A Blood-brain barrier (BBB) opening was performed using a 1 MHz preclinical ultrasound system in combination with 10µl/g microbubbles. Brain penetration of immune checkpoint inhibitors was determined, and immune cell populations were evaluated using flow cytometry. The impact of repeated treatments on survival was determined. In syngeneic GL261-bearing immunocompetent mice, we showed that UMBO safely and repeatedly open the BBB. BBB opening was confirmed visually and microscopically using Evans’s blue dye and magnetic resonance imaging. UMBO plus anti-PDL-1 was associated with a significant improvement of the overall...

2025, arXiv (Cornell University)

Personalized cancer vaccines are envisioned as the next generation rational cancer immunotherapy. The key step in developing personalized therapeutic cancer vaccines is to identify tumor-specific neoantigens that are on the surface of tumor cells. A promising method for this is through de novo peptide sequencing from mass spectrometry data. In this paper we introduce DeepNovoV2, the stateof-the-art model for de novo peptide sequencing 1 . In DeepNovoV2, a spectrum is directly represented as a set of (m/z, intensity) pairs, therefore it does not suffer from the accuracy-speed/memory trade off problem. The model combines an order invariant network structure (T-Net) and recurrent neural networks and provides a complete end-to-end training and prediction framework to sequence patterns of peptides. Our experiments on a wide variety of data from different species show that DeepNovoV2 outperforms previous state-of-the-art methods, achieving 13.01-23.95 % higher accuracy at the peptide level.

2025, Trends in Cancer

high-dose regimes on the hematopoietic compartment, chemotherapy could also have a positive impact by modulating specific immune populations such as regulatory T cells (Tregs), myeloidderived suppressor cells (MDSCs), and immune effector cells. In addition, it is becoming clear that the cancer patient outcome and therapy responses are influenced by the microbiome. Interestingly, the microbiota, and particularly gut bacteria, could also influence the behavior of distant tumor tissue. This role could be mediated, among other mechanisms, by typical pathogen-associated molecular patterns (PAMPs) or by microbial antigens that mimic tumor antigens, thus modulating the cancer-immune interaction. Nonetheless, the 'oncobiome' field is still in early development and needs further experimental authentication, especially in clinical practice. We discuss here an integral perspective of the different strategies that may improve chemoimmunotherapeutic regimes in anticancer therapy.

2025, Frontiers in Cell and Developmental Biology

2025, Texila International Journal of Public Health

Customizing treatments according to each patient's distinct genetic, molecular, and clinical traits, precision medicine holds the potential to completely transform the way cancer is treated. Advances in immunotherapy, liquid biopsy technology, multi-omics, and gene editing methods like CRISPR are all contributing to this strategy. By combining these advancements, it will be possible to develop tailored medicines that focus on the underlying genetic causes of cancer, increasing the precision and efficacy of cancer treatments. Furthermore, machine learning and artificial intelligence provide strong instruments for forecasting therapy outcomes and refining therapeutic approaches. Widespread adoption is still hampered by issues like the intricacy of cancer genetics, the high expense of sophisticated therapies, restricted access in environments with limited resources, and the requirement for uniform clinical data. In order to alter global cancer treatment and improve patient outcomes, it will be imperative to address these issues and guarantee that all patients may benefit from precision medicine.

2025, PLoS ONE

Background: Monoclonal antibodies (mAb) against GD2 ganglioside have been shown to be effective for the treatment of neuroblastoma. Beneficial actions are, however, associated with generalized pain due to the binding of anti-GD2 mAbs to peripheral nerve fibers followed by complement activation. Neuroblastoma cells that express GD2 also express its O-acetyl derivative, O-acetyl-GD2 ganglioside (OAcGD2). Hence, we investigated the distribution of OAcGD2 in human tissues using mAb 8B6 to study the cross-reactivity of mAb 8B6 with human tissues. Methodology/Principal Findings: The distribution of OAcGD2 was performed in normal and malignant tissues using an immunoperoxydase technique. Anti-tumor properties of mAb 8B6 were studied in vitro and in vivo in a transplanted tumor model in mice. We found that OAcGD2 is not expressed by peripheral nerve fibers. Furthermore, we demonstrated that mAb 8B6 was very effective in the in vitro and in vivo suppression of the growth of tumor cells. Importantly, mAb 8B6 anti-tumor efficacy was comparable to that of mAb 14G2a specific to GD2. Conclusion/Significance: Development of therapeutic antibodies specific to OAcGD2 may offer treatment options with reduced adverse side effects, thereby allowing dose escalation of antibodies.

2025, Frontiers in Molecular Biosciences

Melanoma is the deadliest type of skin cancer with steadily increasing incidence worldwide during the last few decades. In addition to its tumor associated antigens (TAAs), melanoma has a high mutation rate compared to other tumors, which promotes the appearance of tumor specific antigens (TSAs) as well as increased lymphocytic infiltration, inviting the use of therapeutic tools that evoke new or restore pre-existing immune responses. Innovative therapeutic proposals, such as immune checkpoint inhibitors (ICIs), have emerged as effective options for melanoma. However, a significant portion of these patients relapse and become refractory to treatment. Likewise, strategies using viral vectors, replicative or not, have garnered confidence and approval by different regulatory agencies around the world. It is possible that further success of immune therapies against melanoma will come from synergistic combinations of different approaches. In this review we outline molecular features inhe...

2025, Nature Immunology

Transforming growth factor beta (TGFβ) and activin A suppress natural killer (NK) cell function and proliferation, limiting the efficacy of adoptive NK cell therapies. Inspired by the partial resistance to TGFβ of NK cells with SMAD4 haploinsufficiency, we used CRISPR-Cas9 for knockout of SMAD4 in human NK cells. Here we show that SMAD4 KO NK cells were resistant to TGFβ and activin A inhibition, retaining their cytotoxicity, cytokine secretion and interleukin-2/interleukin-15-driven proliferation. They showed enhanced tumor penetration and tumor growth control, both as monotherapy and in combination with tumor-targeted therapeutic antibodies. Notably, SMAD4 KO NK cells outperformed control NK cells treated with a TGFβ inhibitor, underscoring the benefit of maintaining SMAD4-independent TGFβ signaling. SMAD4 KO conferred TGFβ resistance across diverse NK cell platforms, including CD19-CAR NK cells, stem cell-derived NK cells and ADAPT-NK cells. These findings position SMAD4 knockout as a versatile and compelling strategy to enhance NK cell antitumor activity, providing a new avenue for improving NK cell-based cancer immunotherapies. Allogeneic NK cell adoptive transfer following hematopoietic stem cell transplantation exhibits promising graft-versus-leukemia efficacy and a favorable safety profile 1 . Although allogeneic NK cell therapies, including chimeric antigen receptor (CAR)-NK cells, have shown clinical benefits in certain hematological malignancies 1,2 , their clinical efficacy in solid tumors remains limited , due to their inefficient homing and function in the tumor microenvironment (TME) . Most solid tumors are poorly permeable to NK cells, partially due to the influence of TGFβ, a suppressive cytokine produced by tumor cells and other regulatory cells in the TME . Active TGFβ binds to TGFβ type 2 receptor dimers (TGFβRII), which then recruit and activate type 1 receptors (TGFβRI) to form a tetrameric receptor complex. The canonical signaling initiates with the phosphorylation of SMAD2 and SMAD3 receptor-SMADs (R-SMADs), which subsequently complex with SMAD4 and translocate to the nucleus, where they regulate the activity of cell-type-specific transcription factors, co-activators and co-repressors 8 . Additionally, SMAD2/SMAD3 can interact with alternative partners, including transcriptional intermediary factor 1 gamma (TIF1γ or TRIM33), IKKα or DROSHA, modulating TGFβ-dependent cell proliferation and motility in hematopoietic or epithelial cells . Beyond

2025, World Academy of Sciences journal

For several decades, surgery, chemotherapy and radiation therapy have been the fundamental components of cancer treatment. Although these represent key therapeutic strategies, novel forms of medical treatment recently triggered an improvement in the methods with which cancer sufferers are being treated, namely with chimeric antigen receptor (CAR) T-cells. CAR T-cell immunotherapy is all set for serving the new prospect in cancer treatment. It utilizes the underlying immune potential to enhance the T-cell antigen recognition property and minimize the cytotoxicity level by engineering. CAR T-cell immunotherapy exerts minimal side-effects compared to the other available methods, such as hematological and solid cancer treatment. The Food and Drug Administration approved these 'biologically active living drugs' and highlighted the impact of this immunotherapy. Therefore, scientists are working to produce highly efficient CAR T-cells with minimal side-effects. The present review discusses the role of various generations, including the next generation of the CAR T-cells, their significance and the effects on cancer patients. Contents 1. Introduction 2. Reasons for the use of CAR T-cell immunotherapy 3. The CAR T-cell generations 4. Positive impact of CAR T-cell immunotherapy on patients 5. Post-therapy challenges and their management 6. Next-generation CAR T-cell therapies 7. Challenges and limitations associated with CAR T-cell therapy 8. Conclusions and future perspectives

2025, Scientific Reports

Radiomics studies to predict lymph node (LN) metastasis has only focused on either primary tumor or LN alone. However, combining radiomics features from multiple sources may reflect multiple characteristic of the lesion thereby increasing the discriminative performance of the radiomic model. Therefore, the present study intends to evaluate the efficiency of integrative nomogram, created by combining clinical parameters and radiomics features extracted from gross tumor volume (GTV), peritumoral volume (PTV) and LN, for the preoperative prediction of LN metastasis in clinical cT1N0M0 adenocarcinoma. A primary cohort of 163 patients (training cohort, 113; and internal validation cohort, 50) and an external validation cohort of 53 patients with clinical stage cT1N0M0 were retrospectively included. Features were extracted from three regions of interests (ROIs): GTV; PTV (5.0 mm around the tumor) and LN on pre-operative contrast enhanced computed tomography (CT). LASSO logistic regression...

2025, International Journal of Molecular Sciences

Therapeutic cancer vaccines have become firmly established as a reliable and proficient form of tumor immunotherapy. They represent a promising approach for substantial advancements in the successful treatment of malignant diseases. One attractive vaccine strategy is using, as the vaccine material, the whole tumor cells treated ex vivo by rapid tumor ablation therapies that instigate stress signaling responses culminating in immunogenic cell death (ICD). One such treatment is photodynamic therapy (PDT). The underlying mechanisms and critical elements responsible for the potency of these vaccines are discussed in this review. Radiotherapy has emerged as a suitable component for the combined therapy protocols with the vaccines. Arguments and prospects for optimizing tumor control using a radiovaccination strategy involving X-ray irradiation plus PDT vaccines are presented, together with the findings supporting its validity.

2025, Nature Immunology

T cell exhaustion presents one of the major hurdles to cancer immunotherapy. Among exhausted CD8 + tumor-infiltrating lymphocytes (TILs), the terminally exhausted subset contributes directly to tumor cell killing owing to its cytotoxic effector function. However, this subset does not respond to immune checkpoint blockades and is difficult to be reinvigorated with restored proliferative capacity. Here, we show that a half-life-extended interleukin (IL)-10/Fc fusion protein directly Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

2025, Yusuf Taha ER

Bu yazıda B hücreli lösemilerde işe yarayan CAR T-cell tedavisinin T hücreli lösemilerdeki biyobelirteçlerinin incelendiği makaleyi değerlendirdim.

2025, Cancers

Hepatocellular carcinoma (HCC), a prevalent and often fatal liver cancer, presents significant treatment challenges, especially in its advanced stages. This article delves into the promising approach of combining immunotherapy, particularly immune checkpoint inhibitors, with radiation therapy, a cornerstone of HCC management. Our review synthesizes current preclinical and clinical research, highlighting the potential synergistic effects of this combinational treatment. Emerging evidence suggests that this synergy enhances tumor control and improves patient survival rates. The combination leverages the localized, tumor-targeting ability of radiation therapy and the systemic, immune-boosting effects of immunotherapy, potentially overcoming the limitations inherent in each treatment modality when used separately. This integrative approach is especially promising in addressing the complex tumor microenvironment of HCC. However, the treatment landscape is nuanced, with challenges such as patient-specific response variability and potential resistance to therapies. Future research directions should focus on refining these combination strategies, tailoring them to individual patient profiles, and understanding the underlying mechanisms that govern the interaction between immunotherapy and radiation therapy. Such advancements could significantly improve HCC management, setting new standards for patient care and treatment efficacy.

2025, Current gastroenterology reports

Purpose of Review This review critically examines the latest approaches in treating advanced gastroesophageal malignancies. It emphasizes the significance of angiogenesis as a therapeutic target and discusses the potential synergy of combining angiogenesis inhibitors with immune checkpoint inhibitors (ICIs) to enhance treatment efficacy. Recent Findings Emerging evidence from clinical trials, such as the INTEGRATE IIa trial with regorafenib and studies involving apatinib and sunitinib, underscores the efficacy of targeting the VEGFR pathway. These studies indicate substantial benefits in progression-free survival (PFS) and overall survival (OS) in patients with advanced stages of the disease who have limited treatment options. Additionally, the recent introduction of combination therapies involving ICIs has shown an increased response rate, suggesting a promising direction for future treatment protocols. Summary The landscape of treatment for gastroesophageal malignancies is rapidly evolving. Research is now pivoting from conventional chemotherapy to a more nuanced approach that includes targeted therapy and immunotherapy.

2025, Cancers

In the field of oncology, the Signaling Lymphocyte Activation Molecule (SLAM) family is emerging as pivotal in modulating immune responses within tumor environments. The SLAM family comprises nine receptors, mainly found on immune cell surfaces. These receptors play complex roles in the interaction between cancer and the host immune system. Research suggests SLAM’s role in both enhancing and dampening tumor-immune responses, influencing the progression and treatment outcomes of various cancers. As immunotherapy advances, resistance remains an issue. The nuanced roles of the SLAM family might provide answers. With the rise in technologies like single-cell RNA sequencing and advanced imaging, there is potential for precise SLAM-targeted treatments. This review stresses patient safety, the importance of thorough clinical trials, and the potential of SLAM-focused therapies to transform cancer care. In summary, SLAM’s role in oncology signals a new direction for more tailored and adaptab...

2025

The gut microbiota can mediate the balance between human health and disease, making the microbiome a critical organ. The gut microbiota can locally and systemically regulate the host's immune system. Cancer immunotherapy has evolved as an essential method for treating cancer patients. Rapidly evolving data suggest that the microbiota influences the therapeutic efficacy of immunotherapy, such as immune checkpoint inhibitors. However, the specific effect of the gut microbiota on immunotherapy-treated malignancies remains unclear, and multiple reports have been released with conflicting results. The association between the gut microbiota with cancer immunology and immunotherapy is discussed here, with an emphasis on the relationship with immunotherapy outcomes.

2025, Vaccines

HCC, the most prevalent form of primary liver cancer, presents a substantial global health challenge due to its high mortality and limited therapeutic options. This review delves into the potential of cancer vaccines as a novel therapeutic avenue for HCC. We examine the various categories of cancer vaccines, including peptide-based, dendritic cell-based, viral vector-based, DNA, and mRNA vaccines, and their potential application in HCC management. This review also addresses the inherent challenges in vaccine development, such as tumor heterogeneity and the need for identifying tumor-specific antigens. We underscore the role of cancer vaccines in reshaping the immune environment within HCC, fostering durable immune memory, and their potential in combination therapies. The review also evaluates clinical trials and emphasizes the necessity for more extensive research to optimize vaccine design and patient selection criteria. We conclude with future perspectives, highlighting the signif...

2025, Cancers

The gut microbiome refers to microorganisms and their genetic material influencing local and systemic inflammation. Inflammation is known to contribute to cancer development, progression, and treatment. Evidence suggests that modulating the gut microbiome may affect responses to various cancer therapies. The gut microbiota has been suggested to have an impact on immunotherapy efficacy, especially the currently widely used immune checkpoint inhibitors in various malignancies. Microbial interventions like fecal microbiota transplantation, various probiotics, or even antibiotics can increase or decrease the tumor’s sensitivity to immunotherapy. However, not all tumors react in the same manner, highlighting the tumor microenvironment heterogeneity across tumor types and the influence this has on the crosstalk between the microbiome and therapy outcomes. In this study, we intend to review the association between the gut microbiota and immunotherapy response in cancer patients and the fac...

2025

2025, Clinical and Experimental Medicine

Chronic hepatitis C (CHC) infection is associated with increased TIM-3, PD-1 immune checkpoint receptors expression that inhibits adaptive T cells and increases NK cell cytotoxicity against T helper cells, both resulting T cell exhaustion. Elimination of the virus with direct-acting antivirals (DAAs) may modify host immune response via altering these immune checkpoint receptors’ expression. We conducted a prospective study to analyze changes in TIM-3, PD-1 and their ligands galectin-9, PD-L1 expression by peripheral blood T cell subpopulations, NK cell subpopulations, and monocytes by multicolor flow cytometry in 14 CHC patients successfully treated with 12 weeks of dasabuvir, ombitasvir, and paritaprevir/ritonavir plus ribavirin. Blood samples were collected before, at the end of treatment, and 12 and 24 weeks later. Sustained virological response (SVR) was associated with increased percentage of peripheral blood CD3+ T and CD8+ cytotoxic T lymphocytes and decreased percentage of N...

2025, Int. J. Mol. Sci.

Understanding the modulation of specific immune cells within the tumor microenvironment (TME) offers new hope in cancer treatments, especially in cancer immunotherapies. In recent years, immune modulation and resistance to immunotherapy have become critical challenges in cancer treatments. However, novel strategies for immune modulation have emerged as promising approaches for oncology due to the vital roles of the immunomodulators in regulating tumor progression and metastasis and modulating immunological responses to standard of care in cancer treatments. With the progress in immuno-oncology, a growing number of novel immunomodulators and mechanisms are being uncovered, offering the potential for enhanced clinical immunotherapy in the near future. Thus, gaining a comprehensive understanding of the broader context is essential. Herein, we particularly summarize the paradoxical role of tumor-related immune cells, focusing on how targeted immune cells and their actions are modulated by immunotherapies to overcome immunotherapeutic resistance in tumor cells. We also highlight the molecular mechanisms employed by tumors to evade the long-term effects of immunotherapeutic agents, rendering them ineffective.

2025, Cancers

Despite progress in our understanding of the biology of hepatocellular carcinoma (HCC), this tumour remains difficult-to-cure for several reasons, starting from the particular disease environment where it arises—advanced chronic liver disease—to its heterogeneous clinical and biological behaviour. The advent, and good results, of immunotherapy for cancer called for the evaluation of its potential application also in HCC, where there is evidence of intra-hepatic immune response activation. Several studies advanced our knowledge of immune checkpoints expression in HCC, thus suggesting that immune checkpoint blockade may have a strong rationale even in the treatment of HCC. According to this background, initial studies with tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, and nivolumab, a programmed cell death protein 1 (PD-1) antibody, showed promising results, and further studies exploring the effects of other immune checkpoint inhibitors, alone or with...

2025

Dietary methionine restriction, defined as reduction of methionine intake by around 80%, reproducibly decreases tumor growth and synergizes with cancer therapies. Here, we combined dietary methionine restriction with immune checkpoint inhibitors in a model of colon adenocarcinoma. In vitro, we observed that methionine restriction increased the expression of MHC-I and PD-L1 in both mouse and human colorectal cancer cells. We also saw an increase in the gene expression of STING, a known inducer of type I interferon signaling. Inhibition of the cGAS-STING pathway, pharmacologically or with siRNA, blunted the increase in MHC-I and PD-L1 surface and gene expression following methionine restriction. PD-L1 expression was also This indicated that the cGAS-STING pathway in particular, and interferon in general, is playing a role in the immune response to methionine restriction. We then combined dietary methionine restriction with immune checkpoint inhibitors targeted against CTLA-4 and PD-1 in a MC38 colorectal cancer tumor model in C57BL/6 mice. The combination treatment was five times more effective at reducing tumor size than immune checkpoint inhibition alone in males. We noted sex differences in the response to dietary methionine restriction for the MC38 tumor model in C57BL/6 mice. Finally, we observed an increase in PD-L1 protein expression in MC38 tumors from animals who were fed a methionine-restricted diet. Furthermore, the distribution of CD8 staining changed from mostly peripheric in the controls, to intratumoral in the methioninerestricted tumors. MHC-I, which has a high basal expression in MC38 cells, was highly expressed in all tumors. These results indicate that methionine restriction improves the response to immune checkpoint inhibitors in mice, and that this improvement is associated with the cGAS-STING pathway and interferon signaling. .

2025, Human Pathology

The stage I uterine Malignant Mixed Mullerian Tumor (MMMT) shows different potential for progression. We reason that MMMTs with high grade carcinomatous component and positivity for HB-EGF are prone to recurrence/metastasis in the early stage. A retrospective clinical and histopathologic review with immunohistochemical staining for HB-EGF, EGFR, and integrin-α5 was performed for 62 surgically staged MMMT cases. Recurrence/metastasis (RM) is 6/18(33%) in stage I diseases. Of all the clinicopathologic variables and biomarkers analyzed for stage I MMMT, serous carcinomatous component [83% (5/6) versus 17% (1/12), p=0.0015] and HB-EGF

2025, Cancers

The era of personalized cancer therapy is here. Advances in the field of immunotherapy have paved the way for the development of individualized neoantigen-based therapies that can translate into favorable treatment outcomes and fewer side effects for patients. Addressing challenges related to the identification, access, and clinical application of neoantigens is critical to accelerating the development of individualized immunotherapy for cancer patients.

2025, Regular and Young Investigator Award Abstracts

2025, bioRxiv (Cold Spring Harbor Laboratory)

There is an unmet medical need for new therapeutic approaches and targets for patients with non-Hodgkin lymphoma (NHL) who relapse or are refractory to anti-CD20 immunotherapy. Therefore, we developed a humanized IgG1 antibody targeting CD37, which was tailored to be afucosylated for enhanced antibody-dependent cellular cytotoxicity (ADCC) (NNV024). In line with this, NNV024 induced three-fold more potent ADCC activity against patient-derived chronic lymphocytic leukemia (CLL) cells compared with anti-CD20 obinutuzumab. Moreover, NNV024 showed 2-fold higher ADCC activity than anti-CD20 rituximab and a recombinant version of DuoHexaBody-CD37 against both NHL and CLL cells. Survival was significantly longer after NNV024 treatment than with obinutuzumab in a mouse model. In addition, NNV024 showed a favourable plasma half-life in human FcRn transgenic mice of about 9-days, which was 2-fold longer than that of obinutuzumab and DuoHexaBody-CD37. These results warrant the further development of NNV024 as a treatment for NHL.