颗粒酶B
穿孔素
CD8型
细胞毒性T细胞
CTL公司*
癌症研究
生物
T细胞
颗粒酶
调节性T细胞
免疫学
细胞
肿瘤进展
免疫疗法
肿瘤微环境
免疫系统
癌症
白细胞介素2受体
体外
生物化学
遗传学
作者
Nikoletta Diamantopoulos,Joanna Li,Antoine Bouchard,Loïck Joumier,Saba Mohammaei,Vincent Panneton,Jinsam Chang,Mohan Malleshaiah,Woong‐Kyung Suh
出处
期刊:Journal of Immunology
[The American Association of Immunologists]
日期:2024-07-12
卷期号:213 (5): 753-762
被引量:1
标识
DOI:10.4049/jimmunol.2300154
摘要
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.
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