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


Journal

Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440

Informations de publication

Date de publication:
02 2021
Historique:
received: 14 08 2020
accepted: 14 01 2021
entrez: 27 2 2021
pubmed: 28 2 2021
medline: 19 4 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33637530
pii: 7/9/eabe3348
doi: 10.1126/sciadv.abe3348
pmc: PMC7909889
pii:
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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Auteurs

Amélie Cachot (A)

Department of Oncology and Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, CH-1066, Switzerland.

Mariia Bilous (M)

Department of Oncology and Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, CH-1066, Switzerland.
Swiss Institute of Bioinformatics, Lausanne, CH-1015, Switzerland.

Yen-Cheng Liu (YC)

Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland.

Xiaokang Li (X)

Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland.

Margaux Saillard (M)

Department of Oncology and Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, CH-1066, Switzerland.

Mara Cenerenti (M)

Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, CH-1211, Switzerland.
Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, CH-1066, Switzerland.

Georg Alexander Rockinger (GA)

Department of Oncology and Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, CH-1066, Switzerland.

Tania Wyss (T)

Department of Oncology and Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, CH-1066, Switzerland.
Swiss Institute of Bioinformatics, Lausanne, CH-1015, Switzerland.

Philippe Guillaume (P)

Department of Oncology and Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, CH-1066, Switzerland.

Julien Schmidt (J)

Department of Oncology and Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, CH-1066, Switzerland.

Raphaël Genolet (R)

Department of Oncology and Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, CH-1066, Switzerland.

Giuseppe Ercolano (G)

Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, CH-1211, Switzerland.
Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, CH-1066, Switzerland.

Maria Pia Protti (MP)

Tumor Immunology Unit, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.

Walter Reith (W)

Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, CH-1211, Switzerland.

Kalliopi Ioannidou (K)

Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, CH-1011, Switzerland.

Laurence de Leval (L)

Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, CH-1011, Switzerland.

Joseph A Trapani (JA)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne 3000, Australia.

George Coukos (G)

Department of Oncology and Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, CH-1066, Switzerland.

Alexandre Harari (A)

Department of Oncology and Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, CH-1066, Switzerland.

Daniel E Speiser (DE)

Department of Oncology and Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, CH-1066, Switzerland.

Alexander Mathis (A)

Harvard University, Cambridge, MA, USA.
Center for Neuroprosthetics, Center for Intelligent Systems, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
Brain Mind Institute, School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, CH-1015, Switzerland.

David Gfeller (D)

Department of Oncology and Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, CH-1066, Switzerland.
Swiss Institute of Bioinformatics, Lausanne, CH-1015, Switzerland.

Hatice Altug (H)

Institute of Bioengineering, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, CH-1015, Switzerland.

Pedro Romero (P)

Department of Oncology and Ludwig Institute for Cancer Research, University of Lausanne, Lausanne, CH-1066, Switzerland.

Camilla Jandus (C)

Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, CH-1211, Switzerland. camilla.jandus@unige.ch.
Ludwig Institute for Cancer Research, Lausanne Branch, Lausanne, CH-1066, Switzerland.

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