Antitumor immunity is mediated by Th1 CD4 and CD8 T lymphocytes, which induce tumor-specific cytolysis, whereas Th17 CD4 T cells have been described to promote tumor growth. Here, we explored the influence of IL-17 on the ability of therapeutic vaccines to induce the rejection of tumors in mice using several adjuvants known to elicit either Th1 or Th17-type immunity. Immunization of mice with Th1-adjuvanted vaccine induced high levels of IFN-γ-producing T cells, whereas injection with Th17-promoting adjuvants triggered the stimulation of both IL-17 and IFN-γ-producing T cells. However, despite their capacity to induce strong Th1 responses, these Th17-promoting adjuvants failed to induce the eradication of tumors. In addition, the systemic administration of IL-17A strongly decreases the therapeutic effect of Th1-adjuvanted vaccines in two different tumor models. This suppressive effect correlated with the capacity of systemically delivered IL-17A to inhibit the induction of CD8 T-cell responses. The suppressive effect of IL-17A on the induction of CD8 T-cell responses was abolished in mice depleted of neutrophils, clearly demonstrating the role played by these cells in the inhibitory effect of IL-17A in the induction of antitumor responses. These results demonstrate that even though strong Th1-type responses favor tumor control, the simultaneous activation of Th17 cells may redirect or curtail tumor-specific immunity through a mechanism involving neutrophils. This study establishes that IL-17 plays a detrimental role in the development of an effective antitumor T cell response and thus could strongly affect the efficiency of immunotherapy through the inhibition of CTL responses.
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http://dx.doi.org/10.1080/2162402X.2020.1758606 | DOI Listing |
Gut Microbes
December 2025
Institute for Medical Immunology, Université Libre de Bruxelles, Gosselies, Belgium.
Maternal gut microbiota composition contributes to the status of the neonatal immune system and could influence the early life higher susceptibility to viral respiratory infections. Using a novel protocol of murine maternal probiotic supplementation, we report that perinatal exposure to () or () increases the influenza A/PR8 virus (IAV) clearance in neonates. Following either supplementation, type 1 conventional dendritic cells (cDC1) were amplified in the lymph nodes leading to an enhanced IAV antigen-experienced IFN-γ producing effector CD8 T cells in neonates and IAV-specific resident memory CD8 T cells in adulthood.
View Article and Find Full Text PDFCommun Biol
December 2024
Institut national de la recherche scientifique (INRS)-Centre Armand-Frappier Santé Biotechnologie, 531 boulevard des Prairies, H7V 1M7, Laval, QC, Canada.
We have shown that virus-specific CD4 and CD8 memory T cells (TM) induce autophagy after T cell receptor (TCR) engagement to provide free glutamine and fatty acids, including in people living with HIV-1 (PLWH). These nutrients fuel mitochondrial ATP generation through glutaminolysis and fatty acid oxidation (FAO) pathways, to fulfill the bioenergetic demands for optimal IL-21 and cytotoxic molecule production in CD4 and CD8 cells, respectively. Here, we expand our knowledge on how the metabolic events that occur in the mitochondria of virus-specific TM down-stream of the autophagy are regulated.
View Article and Find Full Text PDFJ Adv Res
December 2024
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong, China. Electronic address:
Introduction: The efficacy of radiotherapy in colorectal cancer (CRC) is often limited by radiation resistance. Ataxia telangiectasia mutated (ATM) is well known for its role in repairing double-strand DNA breaks within the DNA damage response (DDR) pathway. However, whether ATM mediates other mechanisms contributing to radiation resistance remains insufficiently investigated.
View Article and Find Full Text PDFImmunity
December 2024
Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455, USA; Center for Immunology, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:
Tissue-resident memory CD8 T (Trm) cells control infections and cancer and are defined by their lack of recirculation. Because migration is difficult to assess, residence is usually inferred by putative residence-defining phenotypic and gene signature proxies. We assessed the validity and universality of residence proxies by integrating mouse parabiosis, multi-organ sampling, intravascular staining, acute and chronic infection models, dirty mice, and single-cell multi-omics.
View Article and Find Full Text PDFCancer Immunol Immunother
December 2024
Division of Biomedical Informatics, Seoul National University Biomedical Informatics (SNUBI), Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
Immune checkpoint inhibitors have significantly advanced research in oncology and are used to successfully treat patients with bladder cancer (BC). However, as the benefits of programmed death-1/ programmed death-ligand-1 blockade immunotherapy do not extend to all patients with BC, biomarkers are required to improve prognostic stratification. This study aims to identify reliable biomarkers to enhance the prediction of treatment outcomes.
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