γδ T cells in human colon adenocarcinomas comprise mainly Vδ1, Vδ2, and Vδ3 cells with distinct phenotype and function.
Colon cancer
TCRδ chain
Tumour immunity
γδ T cells
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
02 Jul 2024
02 Jul 2024
Historique:
received:
16
01
2024
accepted:
11
06
2024
medline:
2
7
2024
pubmed:
2
7
2024
entrez:
2
7
2024
Statut:
epublish
Résumé
Γδ T cell infiltration into tumours usually correlates with improved patient outcome, but both tumour-promoting and tumoricidal effects of γδ T cells have been documented. Human γδ T cells can be divided into functionally distinct subsets based on T cell receptor (TCR) Vδ usage. Still, the contribution of these different subsets to tumour immunity remains elusive. Here, we provide a detailed γδ T cell profiling in colon tumours, using mass and flow cytometry, mRNA quantification, and TCR sequencing. δ chain usage in both the macroscopically unaffected colon mucosa and tumours varied considerably between patients, with substantial fractions of Vδ1, Vδ2, and non-Vδ1 Vδ2 cells. Sequencing of the Vδ complementarity-determining region 3 showed that almost all non-Vδ1 Vδ2 cells used Vδ3 and that tumour-infiltrating γδ clonotypes were unique for every patient. Non-Vδ1Vδ2 cells from colon tumours expressed several activation markers but few NK cell receptors and exhaustion markers. In addition, mRNA analyses showed that non-Vδ1 Vδ2 cells expressed several genes for proteins with tumour-promoting functions, such as neutrophil-recruiting chemokines, Galectin 3, and transforming growth factor-beta induced. In summary, our results show a large variation in γδ T cell subsets between individual tumours, and that Vδ3 cells make up a substantial proportion of γδ T cells in colon tumours. We suggest that individual γδ T cell composition in colon tumours may contribute to the balance between favourable and adverse immune responses, and thereby also patient outcome.
Identifiants
pubmed: 38953978
doi: 10.1007/s00262-024-03758-7
pii: 10.1007/s00262-024-03758-7
doi:
Substances chimiques
Receptors, Antigen, T-Cell, gamma-delta
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
174Subventions
Organisme : Vetenskapsrådet
ID : 2021-01008
Organisme : Vetenskapsrådet
ID : 55X-13428
Organisme : Cancerfonden
ID : 22-2080
Organisme : Cancerfonden
ID : 130593
Organisme : Swedish gouvernment
ID : 965065
Organisme : Swedish gouvernment
ID : 144381
Informations de copyright
© 2024. The Author(s).
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