Follicular helper-T cells restore CD8+-dependent antitumor immunity and anti-PD-L1/PD-1 efficacy
| العنوان: | Follicular helper-T cells restore CD8+-dependent antitumor immunity and anti-PD-L1/PD-1 efficacy |
|---|---|
| المؤلفون: | Elise Ballot, Christophe Hibos, François Ghiringhelli, David Rageot, Romain Mary, Léa Hampe, Cédric Rébé, Frédérique Végran, Fanny Chalmin, Julie Niogret, Bertrand Routy, Valentin Derangère, Théo Accogli, James A. Harker, Philippe Joubert, Hélène Berger, Marion Thibaudin, Caroline Truntzer |
| المساهمون: | Wellcome Trust |
| المصدر: | Journal for ImmunoTherapy of Cancer, Vol 9, Iss 6 (2021) Journal for Immunotherapy of Cancer |
| بيانات النشر: | BioMed Central, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Adoptive cell transfer, medicine.medical_treatment, Mice, Antineoplastic Agents, Immunological, 0302 clinical medicine, Immunology and Allergy, Cytotoxic T cell, Immune Checkpoint Inhibitors, RC254-282, Brain Neoplasms, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Adoptive Transfer, Gene Expression Regulation, Neoplastic, Treatment Outcome, Cytokine, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Molecular Medicine, CD8-positive T-lymphocytes, Female, immunotherapy, T Follicular Helper Cells, Immunology, Breast Neoplasms, Biology, programmed cell death 1 receptor, 03 medical and health sciences, Immune system, Cell Line, Tumor, medicine, Animals, Humans, B cell, Pharmacology, Gene Expression Profiling, Interleukins, Germinal center, Basic Tumor Immunology, Immunotherapy, Chemokine CXCL13, Xenograft Model Antitumor Assays, 030104 developmental biology, Cancer research, Glioblastoma, CD8 |
| الوصف: | BackgroundT follicular helper cells (Tfh) are essential to shape B cell response during germinal center formation. Tfh accumulation has been reported in various human cancers, with positive or negative prognostic roles. However, the mechanisms explaining the accumulation of Tfh and their role in cancer remain obscure.MethodsIn vitro differentiated and mouse cell sorted Tfh phenotype was evaluated by flow cytometry and quantitative PCR (qPCR). Antitumor effect of Tfh was evaluated by adoptive transfer in different tumor-bearing mice models. The involvement of immune cells, cytokines and chemokines was evaluated, using depleting antibodies. Chemokines and cytokines expression and production were evaluated by qPCR and ELISA. In human, the impact of immune cells and chemokines on survival was evaluated by analyzing transcriptomic data from public databases and from our own patient cohorts.ResultsIn this study, we show that Tfh exert an antitumor immune effect in a CD8+-dependent manner. Tfh produce interleukin-21, which sustains proliferation, viability, cytokine production and cytotoxic functions of exhausted T cells. The presence of Tfh is required for efficacy of antiprogrammed cell death ligand-1 therapy. Tfh accumulate in the tumor bed and draining lymph nodes in different mouse cancer models. This recruitment is due to the capacity of transforming growth factor β to drive Chemokine (C-X-C motif) Ligand 13 expression, a chemoattractant of Tfh, by intratumor CD8+T cells. Accumulation of Tfh and exhausted CD8+T cells predicts cancer outcome in various cancer types. In patients treated with anti-programmed cell death-1 mAb, accumulation of Tfh and CD8+at the tumor site is associated with outcome.ConclusionThis study provides evidence that CD8+/Tfh crosstalk is important in shaping antitumor immune response generated by immunotherapy. |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2816f20bd82a0ea077d0f050a2154042 http://hdl.handle.net/10044/1/89627 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2816f20bd82a0ea077d0f050a2154042 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |