ICOS-expressing Regulatory T Cells Influence the Composition of Antitumor CTL Populations.
J Immunol
; 213(5): 753-762, 2024 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-38995175
ABSTRACT
The role of ICOS in antitumor T cell responses and overall tumor progression has been controversial. In this study, we compared tumor progression in mice lacking ICOS selectively in regulatory T (Treg) cells or in all T cells. Using an experimental melanoma lung metastasis model, we found that Treg cell-specific ICOS knockout reduces the overall tumor burden compared with Cre control mice, with increased CD4+-to-Treg cell and CD8+-to-Treg cell ratios in the tumor. In contrast, there was no difference in the tumor burden in mice lacking ICOS in all of the T cell compartments. This suggests a dual role of ICOS costimulation in promoting protumor and antitumor T cell responses. Consistent with reduced tumor burden, we found that Treg cell-specific deletion of ICOS leads to an increase of CD8+ CTLs that express high levels of granzyme B and perforin. Moreover, single-cell transcriptome analysis revealed an increase of Ly108+Eomeshi CD8+ T cells at the cost of the Ly108+T-bethi subset in Treg cell-specific knockout mice. These results suggest that ICOS-expressing Treg cells suppress the CTL maturation process at the level of Eomes upregulation, a critical step known to drive perforin expression and cytotoxicity. Collectively, our data imply that cancer immunotherapies using ICOS agonist Abs may work better in Treg cell-low tumors or when they are combined with regimens that deplete tumor-infiltrating Treg cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Melanoma Experimental
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Linfócitos T Citotóxicos
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Linfócitos T Reguladores
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Camundongos Knockout
/
Proteína Coestimuladora de Linfócitos T Induzíveis
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Canadá
País de publicação:
Estados Unidos