Scientific article
Open access

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

Published inScience Advances, vol. 7, no. 9, eabe3348
Publication date2021

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.

  • Swiss National Science Foundation - PRIMA PR00P3_179727
Citation (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
Main files (1)
Article (Published version)
Secondary files (1)
ISSN of the journal2375-2548

Technical informations

Creation03/02/2021 9:01:00 AM
First validation03/02/2021 9:01:00 AM
Update time03/16/2023 12:11:28 AM
Status update03/16/2023 12:11:26 AM
Last indexation10/19/2023 2:53:05 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack