PD-1 and TIM-3 differentially regulate subsets of mouse IL-17A-producing γδ T cells.
J Exp Med
; 220(2)2023 02 06.
Article
em En
| MEDLINE
| ID: mdl-36480166
ABSTRACT
IL-17A-producing γδ T cells in mice consist primarily of Vγ6+ tissue-resident cells and Vγ4+ circulating cells. How these γδ T cell subsets are regulated during homeostasis and cancer remains poorly understood. Using single-cell RNA sequencing and flow cytommetry, we show that lung Vγ4+ and Vγ6+ cells from tumor-free and tumor-bearing mice express contrasting cell surface molecules as well as distinct co-inhibitory molecules, which function to suppress their expansion. Vγ6+ cells express constitutively high levels of PD-1, whereas Vγ4+ cells upregulate TIM-3 in response to tumor-derived IL-1ß and IL-23. Inhibition of either PD-1 or TIM-3 in mammary tumor-bearing mice increased Vγ6+ and Vγ4+ cell numbers, respectively. We found that genetic deletion of γδ T cells elicits responsiveness to anti-PD-1 and anti-TIM-3 immunotherapy in a mammary tumor model that is refractory to T cell checkpoint inhibitors, indicating that IL-17A-producing γδ T cells instigate resistance to immunotherapy. Together, these data demonstrate how lung IL-17A-producing γδ T cell subsets are differentially controlled by PD-1 and TIM-3 in steady-state and cancer.
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1
Base de dados:
MEDLINE
Assunto principal:
Subpopulações de Linfócitos T
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Interleucina-17
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Receptor de Morte Celular Programada 1
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Receptor Celular 2 do Vírus da Hepatite A
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Neoplasias
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article