Harnessing dendritic cells in cancer (original) (raw)
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Insights Into Dendritic Cells in Cancer Immunotherapy: From Bench to Clinical Applications
Frontiers in Cell and Developmental Biology, 2021
Dendritic cells (DCs) are efficient antigen-presenting cells (APCs) and potent activators of naïve T cells. Therefore, they act as a connective ring between innate and adaptive immunity. DC subsets are heterogeneous in their ontogeny and functions. They have proven to potentially take up and process tumor-associated antigens (TAAs). In this regard, researchers have developed strategies such as genetically engineered or TAA-pulsed DC vaccines; these manipulated DCs have shown significant outcomes in clinical and preclinical models. Here, we review DC classification and address how DCs are skewed into an immunosuppressive phenotype in cancer patients. Additionally, we present the advancements in DCs as a platform for cancer immunotherapy, emphasizing the technologies used for in vivo targeting of endogenous DCs, ex vivo generated vaccines from peripheral blood monocytes, and induced pluripotent stem cell-derived DCs (iPSC-DCs) to boost antitumoral immunity.
Perspectives on Reprograming Cancer-Associated Dendritic Cells for Anti-Tumor Therapies
Frontiers in Oncology, 2014
In recent years, the relevance of the tumor microenvironment (TME) in the progression of cancer has gained considerable attention. It has been shown that the TME is capable of inactivating various components of the immune system responsible for tumor clearance, thus favoring cancer cell growth and tumor metastasis. In particular, effects of the TME on antigen-presenting cells, such as dendritic cells (DCs) include rendering these cells unable to promote specific immune responses or transform them into suppressive cells capable of inducing regulatory T cells. In addition, under the influence of the TME, DCs can produce growth factors that induce neovascularization, therefore further contributing to tumor development. Interestingly, cancer-associated DCs harbor tumor antigens and thus have the potential to become anti-tumor vaccines in situ if properly reactivated. This perspective article provides an overview of the scientific background and experimental basis for reprograming cancer-associated DCs in situ to generate anti-tumor immune responses.
Trial watch: Dendritic cell-based interventions for cancer therapy
Oncoimmunology, 2012
Dendritic cells (DCs) occupy a central position in the immune system, orchestrating a wide repertoire of responses that span from the development of self-tolerance to the elicitation of potent cellular and humoral immunity. Accordingly, DCs are involved in the etiology of conditions as diverse as infectious diseases, allergic and autoimmune disorders, graft rejection and cancer. During the last decade, several methods have been developed to load DCs with tumor-associated antigens, ex vivo or in vivo, in the attempt to use them as therapeutic anticancer vaccines that would elicit clinically relevant immune responses. While this has not always been the case, several clinical studies have demonstrated that DC-based anticancer vaccines are capable of activating tumor-specific immune responses that increase overall survival, at least in a subset of patients. In 2010, this branch of clinical research has culminated with the approval by FDA of a DC-based therapeutic vaccine (sipuleucel-T, ...
Dendritic cells and cancer immunotherapy
Current Opinion in Immunology, 2014
Dendritic cells (DC) play an essential role in the induction and regulation of immune responses, including the generation of cytotoxic T lymphocytes (CTL) for the eradication of cancers. DC-based cancer vaccines are well tolerated with few side effects and can generate anti-tumour immune responses, but overall they have been of limited benefit. Recent studies have demonstrated that CD141(+) DC play an important role in anti-tumour responses. These are now attractive targets for the development of vaccines that directly target DC in vivo. An understanding of the functional specialisations of DC subsets, strategies for the delivery of tumour Ag to DC and for enhancing immune responses, point to promising new avenues for the design of more effective DC-based cancer vaccines.
Dendritic cell-based interventions for cancer therapy
Citation: Vacchelli E, Vitale I, Eggermont A, Fridman WH, Fučíková J, Cremer I, et al. Trial Watch: Dendritic cell-based interventions for cancer therapy. OncoImmunology 2013; 2:e25771; http://dx.doi.org/10.4161/
Dendritic cells in cancer immunotherapy: vaccines and combination immunotherapies
Expert Review of Vaccines, 2013
Dendritic cells (DCs) are specialized immunostimulatory cells involved in the induction and regulation of immune responses. The feasibility of large-scale ex vivo generation of DCs from patients' monocytes allows for therapeutic application of ex vivo-cultured DCs to bypass the dysfunction of endogenous DCs, restore immune surveillance, induce cancer regression or stabilization or delay or prevent its recurrence. While the most common paradigm of the therapeutic application of DCs reflects their use as cancer 'vaccines', additional and potentially more effective possibilities include the use of patients' autologous DCs as parts of more comprehensive therapies involving in vivo or ex vivo induction of tumor-reactive T cells and the measures to counteract systemic and local immunosuppression in tumor-bearing hosts. Ex vivocultured DCs can be instructed to acquire distinct functions relevant for the induction of effective cancer immunity (DC polarization), such as the induction of different effector functions or different homing properties of tumor-specific T cells (delivery of 'signal 3' and 'signal 4'). These considerations highlight the importance of the application of optimized conditions for the ex vivo culture of DCs and the potential combination of DC therapies with additional immune interventions to facilitate the entry of DC-induced T cells to tumor tissues and their local antitumor functions.
Dendritic cells in cancer immunology and immunotherapy
Nature Reviews Immunology, 2019
Cancers originate from the uncontrolled proliferative activity of the organism's cells and present characteristic hallmarks 1. Despite their self-origin, tumours can induce immune responses. However, the incomplete elimination of tumour cells by the immune system can result in the persistence of 'immune-edited' tumours that are not efficiently cleared by the immune system 2. The association of infections with spontaneous tumour regression and the capacity of the immune system to reject immunogenic tumours in preclinical models 1 support the role of the immune system in protection against cancers. Moreover, large-scale projects such as The Cancer Genome Atlas and the Immunoprofiler Initiative have identified tumour-infiltrating immune cells-either through gene-expression signatures 3-6 or by direct observation of these cell types 7-as important correlates of cancer prognosis and treatment responsiveness. Although dendritic cells (DCs) constitute a rare immune cell population within tumours and lymphoid organs, these cells are central for the initiation of antigen-specific immunity and tolerance 8. Therefore, manipulation of DCs holds great potential for inducing efficient antitumour immunity 8. DCs promote immunity or tolerance by sampling and presenting antigens to T cells and by providing immunomodulatory signals through cell-cell contacts and cytokines 9,10. DC functions are determined by their integration of environmental signals, which are sensed via surfaceexpressed and intracellular receptors for cytokines, pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) 11. Recent data highlight the specific roles of DC subsets in antitumour immunity, with key implications for therapy 12,13. In that regard, most of our general understanding of DC subsets and functions is based on observations in mouse models, and, currently, increasing efforts aim to evaluate the biology of human DCs. In this Review, we will discuss the main functions of DCs in cancer immunology and consider the therapeutic potential of targeting DCs in patients with cancer.
Current Medicinal Chemistry, 2006
Existence of residual cancers and recurrence of cancers are two major limitations of conventional therapies against cancers. A naturally-occurring defense system against tumor may be established in cancer patients by induction of antitumor immunity. Both polyvalent and tumor antigen-defined vaccines have been administered to cancer patients to accomplish this. However, the efficacy of these approaches is not promising. Dendritic cells (DCs) are regulator of the immune system. Antigens loaded on DCs (antigen-pulsed DCs) are able to induce immune responses when this can not be achieved by administration of antigens or vaccines only. Tumor antigen-pulsed DCs are now used for treatment of patients with cancers. But, it is unlikely that the present regimen of DC-based therapy would be an independent anticancer therapeutic approach. However, the therapeutic potentials of tumor antigen-pulsed DCs can be accentuated in cancer patients if this immune therapy is performed as part of multidisciplinary therapeutic approaches. In this review, we will describe about the concept and limitations of the present regimen of tumor antigen-pulsed DC-based therapy in cancer patients. We will further discuss how DC-based therapy can be applied as a multidisciplinary approach to cancer treatment.
Dendritic Cell Based Cancer Therapy
2012
Dendritic cells (DCs) occupy a central position in the immune system, orchestrating a wide repertoire of responses that span from the development of self-tolerance to the elicitation of potent cellular and humoral immunity. Accordingly, DCs are involved in the etiology of conditions as diverse as infectious diseases, allergic and autoimmune disorders, graft rejection and cancer. During the last decade, several methods have been developed to load DCs with tumor-associated antigens, ex vivo or in vivo, in the attempt to use them as therapeutic anticancer vaccines that would elicit clinically relevant immune responses. While this has not always been the case, several clinical studies have demonstrated that DCbased anticancer vaccines are capable of activating tumorspecific immune responses that increase overall survival, at least in a subset of patients. In 2010, this branch of clinical research has culminated with the approval by FDA of a DCbased therapeutic vaccine (sipuleucel-T, Provenge ®) for use in patients with asymptomatic or minimally symptomatic metastatic hormone-refractory prostate cancer. Intense research efforts are currently dedicated to the identification of the immunological features of patients that best respond
Optimizing dendritic cell-based approaches for cancer immunotherapy
The Yale journal of biology and medicine, 2014
Dendritic cells (DC) are professional antigen-presenting cells uniquely suited for cancer immunotherapy. They induce primary immune responses, potentiate the effector functions of previously primed T-lymphocytes, and orchestrate communication between innate and adaptive immunity. The remarkable diversity of cytokine activation regimens, DC maturation states, and antigen-loading strategies employed in current DC-based vaccine design reflect an evolving, but incomplete, understanding of optimal DC immunobiology. In the clinical realm, existing DC-based cancer immunotherapy efforts have yielded encouraging but inconsistent results. Despite recent U.S. Federal and Drug Administration (FDA) approval of DC-based sipuleucel-T for metastatic castration-resistant prostate cancer, clinically effective DC immunotherapy as monotherapy for a majority of tumors remains a distant goal. Recent work has identified strategies that may allow for more potent "next-generation" DC vaccines. Add...