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Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer

Bilous, Mariia
Liu, Yen-Cheng
Li, Xiaokang
Saillard, Margaux
Rockinger, Georg Alexander
Wyss, Tania
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Published in Science advances. 2021, vol. 7, no. 9, eabe3348
Abstract CD4 T cells have been implicated in cancer immunity for their helper functions. Moreover, their direct cytotoxic potential has been shown in some patients with cancer. Here, by mining single-cell RNA-seq datasets, we identified CD4 T cell clusters displaying cytotoxic phenotypes in different human cancers, resembling CD8 T cell profiles. Using the peptide-MHCII-multimer technology, we confirmed ex vivo the presence of cytolytic tumor-specific CD4 T cells. We performed an integrated phenotypic and functional characterization of these cells, down to the single-cell level, through a high-throughput nanobiochip consisting of massive arrays of picowells and machine learning. We demonstrated a direct, contact-, and granzyme-dependent cytotoxic activity against tumors, with delayed kinetics compared to classical cytotoxic lymphocytes. Last, we found that this cytotoxic activity was in part dependent on SLAMF7. Agonistic engagement of SLAMF7 enhanced cytotoxicity of tumor-specific CD4 T cells, suggesting that targeting these cells might prove synergistic with other cancer immunotherapies.
PMID: 33637530
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Research group Ciblage des lymphocytes sécrétant des cytokines (1015)
Swiss National Science Foundation: PRIMA PR00P3_179727
(ISO format)
CACHOT, Amélie et al. Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer. In: Science Advances, 2021, vol. 7, n° 9, p. eabe3348. doi: 10.1126/sciadv.abe3348 https://archive-ouverte.unige.ch/unige:149948

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Deposited on : 2021-03-02

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