Journal article

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

Amelie Cachot, Mariia Bilous, Yen-Cheng Liu, Xiaokang Li, Margaux Saillard, Mara Cenerenti, Georg Alexander Rockinger, Tania Wyss, Philippe Guillaume, Julien Schmidt, Raphael Genolet, Giuseppe Ercolano, Maria Pia Protti, Walter Reith, Kalliopi Ioannidou, Laurence de Leval, Joseph A Trapani, George Coukos, Alexandre Harari, Daniel E Speiser Show all

SCIENCE ADVANCES | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2021

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 dir..

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Grants

Awarded by Swiss National Science Foundation


Funding Acknowledgements

We thank the following funding that supported this work: the ISREC Foundation (to A.C., Y.-C.L., and H.A.), the MEDIC Foundation (to C.J.), the Fondazione San Salvatore (to C.J.), the Swiss National Science Foundation (PRIMA PR00P3_179727 to C.J., SNF 310030-182735 to P.R., and 31003A_173156 to D.G.), the Olga Mayenfish Foundation (to C.J.), the Chan Zuckerberg Initiative (to A.M.), the Taiwan EPFL PhD scholarship (to Y.-C.L.), and the Ludwig Institute for Cancer Research. This project has received funding from the Societe Academique Vaudoise-Fonds Novartis Consumer Health (to C.J. and H.A.).