Iole Macchia - Academia.edu (original) (raw)

Papers by Iole Macchia

Immunology, Oct 1, 2006

Circulating CD4 + CD8 + T lymphocytes have been described in the peripheral blood of humans and s... more Circulating CD4 + CD8 + T lymphocytes have been described in the peripheral blood of humans and several animal species. However, the origin and functional properties of these cells remain poorly understood. In the present study, we evaluated the frequency, phenotype and function of peripheral CD4 + CD8 + T cells in rhesus macaques. Two distinct populations of CD4 + CD8 + T cells were identified: the dominant one was CD4 hi CD8 lo and expressed the CD8aa homodimer, while the minor population was CD4 lo CD8 hi and expressed the CD8ab heterodimer. The majority of CD4 hi CD8a lo T cells exhibited an activated effector/memory phenotype (CCR5 lo CD7-CD28-HLA-DR +) and expressed relatively high levels of granzyme B. Intracellular cytokine staining assays demonstrated that the frequency of cytomegalovirus-specific T cells was enriched five-fold in CD4 hi CD8a lo T cells compared to single-positive CD4 + T cells, whereas no consistent enrichment was observed for simian immunodeficiency virus (SIV)-specific T cells. Cross-sectional studies of SIV-infected animals demonstrated that the frequency of CD4 hi CD8a lo T cells was lower in wild-type SIV-infected animals compared to uninfected controls, although prospective studies of SIV-infected animals demonstrated depletion of CD4 hi CD8a lo lymphocytes only in a subset of animals. Taken together, these data suggest that CD4 + T cells expressing CD8a represent an effector/memory subset of CD4 + T cells and that this cell population can be depleted during the course of SIV infection.

BioMed Research International, 2013

The development of immune monitoring assays is essential to determine the immune responses agains... more The development of immune monitoring assays is essential to determine the immune responses against tumor-specific antigens (TSAs) and tumor-associated antigens (TAAs) and their possible correlation with clinical outcome in cancer patients receiving immunotherapies. Despite the wide range of techniques used, to date these assays have not shown consistent results among clinical trials and failed to define surrogate markers of clinical efficacy to antitumor vaccines. Multiparameter flow cytometry-(FCM-) based assays combining different phenotypic and functional markers have been developed in the past decade for informative and longitudinal analysis of polyfunctional T-cells. These technologies were designed to address the complexity and functional heterogeneity of cancer biology and cellular immunity and to define biomarkers predicting clinical response to anticancer treatment. So far, there is still a lack of standardization of some of these immunological tests. The aim of this review is to overview the latest technologies for immune monitoring and to highlight critical steps involved in some of the FCM-based cellular immune assays. In particular, our laboratory is focused on melanoma vaccine research and thus our main goal was the validation of a functional multiparameter test (FMT) combining different functional and lineage markers to be applied in clinical trials involving patients with melanoma.

Frontiers in Immunology, Jul 6, 2023

Eosinophils are bone marrow-derived granulocytes that, under homeostatic conditions, account for ... more Eosinophils are bone marrow-derived granulocytes that, under homeostatic conditions, account for as much as 1-3% of peripheral blood leukocytes. During inflammation, eosinophils can rapidly expand and infiltrate inflamed tissues, guided by cytokines and alarmins (such as IL-33), adhesion molecules and chemokines. Eosinophils play a prominent role in allergic asthma and parasitic infections. Nonetheless, they participate in the immune response against respiratory viruses such as respiratory syncytial virus and influenza. Notably, respiratory viruses are associated with asthma exacerbation. Eosinophils release several molecules endowed with antiviral activity, including cationic proteins, RNases and reactive oxygen and nitrogen species. On the other hand, eosinophils release several cytokines involved in homeostasis maintenance and Th2-related inflammation. In the context of SARS-CoV-2 infection, emerging evidence indicates that eosinophils can represent possible bloodbased biomarkers for diagnosis, prognosis, and severity prediction of disease. In particular, eosinopenia seems to be an indicator of severity among patients with COVID-19, whereas an increased eosinophil count is associated with a better prognosis, including a lower incidence of complications and mortality. In the present review, we provide an overview of the role and plasticity of eosinophils focusing on various respiratory viral infections and in the context of viral and allergic disease comorbidities. We will discuss the potential utility of eosinophils as prognostic/predictive immune biomarkers in emerging respiratory viral diseases, particularly COVID-19. Finally, we will revisit some of the relevant methods and tools that have contributed to the advances in the dissection of various eosinophil subsets in different pathological settings for future biomarker definition.

Supplementary Methods and Materials from Unraveling Cancer Chemoimmunotherapy Mechanisms by Gene ... more Supplementary Methods and Materials from Unraveling Cancer Chemoimmunotherapy Mechanisms by Gene and Protein Expression Profiling of Responses to Cyclophosphamide

Supplementary Table 1 from Unraveling Cancer Chemoimmunotherapy Mechanisms by Gene and Protein Ex... more Supplementary Table 1 from Unraveling Cancer Chemoimmunotherapy Mechanisms by Gene and Protein Expression Profiling of Responses to Cyclophosphamide

Supplementary Table 2 from Unraveling Cancer Chemoimmunotherapy Mechanisms by Gene and Protein Ex... more Supplementary Table 2 from Unraveling Cancer Chemoimmunotherapy Mechanisms by Gene and Protein Expression Profiling of Responses to Cyclophosphamide

Supplementary Figures 1-7 from Unraveling Cancer Chemoimmunotherapy Mechanisms by Gene and Protei... more Supplementary Figures 1-7 from Unraveling Cancer Chemoimmunotherapy Mechanisms by Gene and Protein Expression Profiling of Responses to Cyclophosphamide

Cancer Research, May 15, 2011

Certain chemotherapeutic drugs, such as cyclophosphamide (CTX), can enhance the antitumor efficac... more Certain chemotherapeutic drugs, such as cyclophosphamide (CTX), can enhance the antitumor efficacy of immunotherapy because of their capacity to modulate innate and adaptive immunity. Indeed, it has been argued that this capacity may be more significant to chemotherapeutic efficacy in general than is currently appreciated. To gain insights into the core mechanisms of chemoimmunotherapy, we methodically profiled the effects of CTX on gene expression in bone marrow, spleen, and peripheral blood, and on cytokine expression in plasma and bone marrow of tumor-bearing mice. Gene and protein expression were modulated early and transiently by CTX, leading to upregulation of a variety of immunomodulatory factors, including danger signals, pattern recognition receptors, inflammatory mediators, growth factors, cytokines, chemokines, and chemokine receptors. These factors are involved in sensing CTX myelotoxicity and activating repair mechanisms, which, in turn, stimulate immunoactivation events that promote efficacy. In particular, CTX induced a T-helper 17 (Th17)-related gene signature associated with an increase in Th17, Th1, and activated CD25 þ CD4 þ Foxp3 À T lymphocytes and a slight recovery of regulatory T cells. By analyzing gene and protein expression kinetics and their relationship to the antitumor efficacy of different therapeutic schedules of combination, we determined that optimal timing for performing adoptive immunotherapy is approximately 1 day after CTX treatment. Together, our findings highlight factors that may propel the efficacy of chemoimmunotherapy, offering a mechanistic glimpse of the important immune modulatory effects of CTX. Cancer Res; 71(10); 3528-39. Ó2011 AACR.

Journal of Medical Primatology, Aug 1, 2007

Background Vaccine combining structural and regulatory proteins is an emerging approach to devel... more Background Vaccine combining structural and regulatory proteins is an emerging approach to develop an HIV/AIDS vaccine and therefore, the immunogenicity and efficacy of two regimens of immunization combining structural (Gag/Pol, Env) and regulatory (Rev, Tat, Nef) Simian immunodeficiency virus (SIV) proteins were compared in cynomolgus monkeys.Methods Monkeys were immunized with Modified Vaccine Ankara vector (MVA‐J5) (protocol 1) or with DNA, Semliki forest virus and MVA vectors (DNA/SFV/MVA) (protocol 2). At week 32, all monkeys were challenge intravenously (protocol 1) or intrarectally (protocol 2) with 50 MID50 of SIVmac251. Humoral, proliferative responses and in particular in protocol 2, the frequency of IFN‐γ producing cells, were measured in all monkeys before and after the challenge.Results Both vaccine regimens elicited humoral and proliferative responses but failed to induce neutralizing antibodies. Upon intravenous challenge, two out of three MVA‐J5 vaccinated monkeys exhibited a long‐term control of the viral replication whereas DNA/SFV/MVA vaccine abrogated the virus replication up to undetectable level in three out of four vaccinated monkeys. A major contribution to this vaccine effect appeared to be the IFN‐γ/ELISPOT responses to vaccine antigens (Gag, Rev Tat and Nef).Conclusions These results, indicate that multiprotein heterologous prime‐boost vaccination can induce a robust vaccine‐induced immunity able to abrogate virus replication.

Supplementary Table 3 from Unraveling Cancer Chemoimmunotherapy Mechanisms by Gene and Protein Ex... more Supplementary Table 3 from Unraveling Cancer Chemoimmunotherapy Mechanisms by Gene and Protein Expression Profiling of Responses to Cyclophosphamide

Supplementary Table 4 from Unraveling Cancer Chemoimmunotherapy Mechanisms by Gene and Protein Ex... more Supplementary Table 4 from Unraveling Cancer Chemoimmunotherapy Mechanisms by Gene and Protein Expression Profiling of Responses to Cyclophosphamide

Virus Research, Jun 1, 2007

Several studies have shown the importance of evaluating Recent Thymic Emigrants (RTEs) by quantif... more Several studies have shown the importance of evaluating Recent Thymic Emigrants (RTEs) by quantification of T cell receptor-rearrangement excision circles (TRECs), as a measure of de novo T cell generation during human immunodeficiency virus-1 (HIV-1) infection. To determine whether acute viral infection may have an impact on TRECs, cynomolgus monkeys (Macaca fascicularis) were infected intrarectally with simian human immunodeficiency virus (SHIV) 89.6P cy11 and the number of signal-joint (sj) TRECs was determined in purified CD4 + and CD8 + populations for up to 28 weeks post-infection. Four weeks after infection, TRECs levels significantly decreased in both CD3 + CD4 + and in CD3 + CD8 + T lymphocytes of infected monkeys, whereas they remained unchanged in uninfected animals. This reduction was followed by a progressive TRECs number recovery in CD3 + CD4 + T lymphocytes that positively correlated with changes in the levels of circulating CD3 + CD4 + T cells. In the CD3 + CD8 + T cell subset, TRECs number remained significantly low and inversely correlated with the increase in the percentages of CD3 + CD8 + T cells. These data suggest that SHIV89.6P cy11 intrarectal infection of cynomolgus monkeys differently affects TRECs content in CD3 + CD4 + and CD3 + CD8 + T cell subsets.

Journal of Medical Primatology, Aug 1, 2001

Effect of vaccination with recombinant modified vaccinia virus Ankara expressing structural and r... more Effect of vaccination with recombinant modified vaccinia virus Ankara expressing structural and regulatory genes of SIV macJ5 on the kinetics of SIV replication in cynomolgus monkeys.

Frontiers in Oncology, Mar 6, 2020

of patients, whereas grade 4 events were not observed. Both treatments induced a significant expa... more of patients, whereas grade 4 events were not observed. Both treatments induced a significant expansion of vaccine-specific CD8 + T cells, with no correlation with the clinical outcome. However, treatment-induced increase of polyfunctionality and of interleukin 2 production by Melan-A-specific CD8 + T cells and expansion/activation of natural killer cells correlated with RFS, being observed only in nonrelapsing patients. Despite the recent availability of different therapeutic options, low-cost, low-toxic therapies with long-lasting clinical effects are still needed in patients with high-risk resected stage III/IV melanoma. The combination of peptide vaccination with IFN-α2b showed a minimal toxicity profile and resulted in encouraging RFS and OS rates, justifying further evaluation in clinical trials, which may include the use of checkpoint inhibitors to further expand the antitumor immune response and the clinical outcome.

Frontiers in immunology, Feb 23, 2024

Frontiers in Immunology

Frontiers in Oncology

IntroductionDespite the recent approval of several therapies in the adjuvant setting of melanoma,... more IntroductionDespite the recent approval of several therapies in the adjuvant setting of melanoma, tumor relapse still occurs in a significant number of completely resected stage III-IV patients. In this context, the use of cancer vaccines is still relevant and may increase the response to immune checkpoint inhibitors. We previously demonstrated safety, immunogenicity and preliminary evidence of clinical efficacy in stage III/IV resected melanoma patients subjected to a combination therapy based on peptide vaccination together with intermittent low-dose interferon-α2b, with or without dacarbazine preconditioning (https://www.clinicaltrialsregister.eu/ctr-search/search, identifier: 2008-008211-26). In this setting, we then focused on pre-treatment patient immune status to highlight possible factors associated with clinical outcome.MethodsMultiparametric flow cytometry was used to identify baseline immune profiles in patients’ peripheral blood mononuclear cells and correlation with the...