Phased Differentiation of γδ T and T CD8 Tumor-infiltrating Lymphocytes Revealed by Single-cell Transcriptomics of Human Cancers

Overview

Journal Oncoimmunology

Specialty Allergy & Immunology

Date 2021 Nov 1

PMID 34721945

Citations 9

Authors

Juan-Pablo Cerapio

Marion Perrier

Camille-Charlotte Balanca

Pauline Gravelle

Frederic Pont

Christel Devaud

Don-Marc Franchini

Virginie Feliu

Marie Tosolini

Carine Valle

Frederic Lopez

Anne Quillet-Mary

Loic Ysebaert

Alejandra Martinez

Jean Pierre Delord

Maha Ayyoub

Camille Laurent

Jean-Jacques Fournie

Affiliations

Soon will be listed here.

Abstract

γδ T lymphocytes diverge from conventional T CD8 lymphocytes for ontogeny, homing, and antigen specificity, but whether their differentiation in tumors also deviates was unknown. Using innovative analyses of our original and ~150 published single-cell RNA sequencing datasets validated by phenotyping of human tumors and murine models, here we present the first high-resolution view of human γδ T cell differentiation in cancer. While γδ T lymphocytes prominently encompass TCRVγ9 cells more differentiated than T CD8 in healthy donor's blood, a different scenario is unveiled in tumors. Solid tumors and lymphomas are infiltrated by a majority of TCRVγnon9 γδ T cells which are quantitatively correlated and remarkably aligned with T CD8 for differentiation, exhaustion, gene expression profile, and response to immune checkpoint therapy. This cancer-wide association is critical for developing cancer immunotherapies.

Citing Articles

γδ T-cells in human malignancies: insights from single-cell studies and analytical considerations.

Ng J, Sze Cheung A Front Immunol. 2024; 15:1438962.

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γδ T cells as unconventional targets of checkpoint blockade.

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Expansion of memory Vδ2 T cells following SARS-CoV-2 vaccination revealed by temporal single-cell transcriptomics.

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Nakashima M, Tanaka Y, Okamura H, Kato T, Imaizumi Y, Nagai K Cells. 2024; 13(2).

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Single-cell spatial explorer: easy exploration of spatial and multimodal transcriptomics.

Pont F, Cerapio J, Gravelle P, Ligat L, Valle C, Sarot E BMC Bioinformatics. 2023; 24(1):30.

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