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Journal for immunotherapy of cancer, 2021-06, Vol.9 (6), p.e002157
2021
Details
- Autor(en) / Beteiligte
- Titel
- Follicular helper-T cells restore CD8+-dependent antitumor immunity and anti-PD-L1/PD-1 efficacy
- Ist Teil von
- Journal for immunotherapy of cancer, 2021-06, Vol.9 (6), p.e002157
- Ort / Verlag
- England: BMJ Publishing Group LTD
- Erscheinungsjahr
- 2021
- Link zum Volltext
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2051-1426eISSN: 2051-1426DOI: 10.1136/jitc-2020-002157Titel-ID: cdi_doaj_primary_oai_doaj_org_article_eb04733954c348f69ad8e9ceaa3f46ea
- Format
- –
- Schlagworte
- Adoptive Transfer, Animals, Antibodies, Antigens, Antineoplastic Agents, Immunological - administration & dosage, Antineoplastic Agents, Immunological - pharmacology, Basic Tumor Immunology, Brain Neoplasms - immunology, Brain Neoplasms - therapy, Breast Neoplasms - genetics, Breast Neoplasms - immunology, Breast Neoplasms - therapy, Cancer, CD8-Positive T-Lymphocytes - metabolism, Cell death, Cell Line, Tumor, Chemokine CXCL13 - genetics, Chemokine CXCL13 - metabolism, Chemokines, Cytokines, Experiments, Female, Flow cytometry, Gene Expression Profiling, Gene Expression Regulation, Neoplastic - drug effects, Glioblastoma - genetics, Glioblastoma - immunology, Glioblastoma - therapy, Humans, Immune Checkpoint Inhibitors - administration & dosage, Immune Checkpoint Inhibitors - pharmacology, Immunotherapy, Interleukins - genetics, Interleukins - metabolism, Ligands, Lung cancer, Lymphatic system, Lymphocytes, Melanoma, Mice, Software, T Follicular Helper Cells - immunology, T Follicular Helper Cells - transplantation, Treatment Outcome, Tumors, Xenograft Model Antitumor Assays