CXCR3型
细胞毒性T细胞
生物
CD8型
T细胞
癌症研究
癌症免疫疗法
免疫学
免疫疗法
树突状细胞
启动(农业)
趋化因子受体
交叉展示
抗原提呈细胞
免疫系统
趋化因子
植物
生物化学
体外
发芽
作者
Mariela A. Moreno Ayala,Timothy F. Campbell,Chenyu Zhang,Noa Dahan,Alissa Bockman,Varsha Prakash,Lawrence Feng,Theo Sher,Michel DuPage
出处
期刊:Immunity
[Elsevier]
日期:2023-07-01
卷期号:56 (7): 1613-1630.e5
被引量:21
标识
DOI:10.1016/j.immuni.2023.06.003
摘要
Infiltration of regulatory T (Treg) cells, an immunosuppressive population of CD4+ T cells, into solid cancers represents a barrier to cancer immunotherapy. Chemokine receptors are critical for Treg cell recruitment and cell-cell interactions in inflamed tissues, including cancer, and thus are an ideal therapeutic target. Here, we show in multiple cancer models that CXCR3+ Treg cells were increased in tumors compared with lymphoid tissues, exhibited an activated phenotype, and interacted preferentially with CXCL9-producing BATF3+ dendritic cells (DCs). Genetic ablation of CXCR3 in Treg cells disrupted DC1-Treg cell interactions and concomitantly increased DC-CD8+ T cell interactions. Mechanistically, CXCR3 ablation in Treg cells increased tumor antigen-specific cross-presentation by DC1s, increasing CD8+ T cell priming and reactivation in tumors. This ultimately impaired tumor progression, especially in combination with anti-PD-1 checkpoint blockade immunotherapy. Overall, CXCR3 is shown to be a critical chemokine receptor for Treg cell accumulation and immune suppression in tumors.
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