Journal
ONCOIMMUNOLOGY
Volume 10, Issue 1, Pages -Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2021.1939518
Keywords
Gamma-delta lymphocyte; scRNAseq; differentiation
Categories
Funding
- Institut National de la Sante et de la Recherche Medicale (INSERM)
- Universite Toulouse III-Paul Sabatier
- Centre National de la Recherche Scientifique (CNRS)
- Laboratoire d'Excellence Toulouse Cancer (TOUCAN-2) [ANR11-LABX]
- Fondation ARC [PGA1-RF2019-0208691]
- Institut Universitaire du Cancer de Toulouse-Oncopole
- Institut Carnot Lymphome
- Fondation ARC pour la Recherche sur le Cancer [PGA1 RF20190208691]
- Institut Carnot CALYM [RAC21009BA]
- LabEx Toulouse Cancer [ANR11-LABX]
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This study provides the first detailed view of human gamma delta T cell differentiation in cancer, revealing a different differentiation pattern from healthy state. The majority of infiltrating T cells in solid tumors and lymphomas are TCRV gamma non9 gamma delta T cells, which shows quantitative correlation and remarkable alignment with T CD8 in terms of differentiation, exhaustion, gene expression profile, and response to immune checkpoint therapy, highlighting the importance of this cancer-wide association for developing cancer immunotherapies.
gamma delta 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 similar to 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 gamma delta T cell differentiation in cancer. While gamma delta T lymphocytes prominently encompass TCRV gamma 9 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 TCRV gamma non9 gamma delta 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.
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