serval:BIB_7FDE10B2A046
Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer.
10.1126/sciadv.abe3348
000622481300027
33637530
Cachot
A.
author
Bilous
M.
author
Liu
Y.C.
author
Li
X.
author
Saillard
M.
author
Cenerenti
M.
author
Rockinger
G.A.
author
Wyss
T.
author
Guillaume
P.
author
Schmidt
J.
author
Genolet
R.
author
Ercolano
G.
author
Protti
M.P.
author
Reith
W.
author
Ioannidou
K.
author
de Leval
L.
author
Trapani
J.A.
author
Coukos
G.
author
Harari
A.
author
Speiser
D.E.
author
Mathis
A.
author
Gfeller
D.
author
Altug
H.
author
Romero
P.
author
Jandus
C.
author
article
2021-02
Science advances
2375-2548
2375-2548
journal
7
9
eabe3348
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.
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cytotoxicity, Immunologic
Humans
Immunotherapy
Neoplasms
T-Lymphocytes, Cytotoxic
eng
60_published
true
peer-reviewed
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
University of Lausanne
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