小柯机器人

美国加州大学Michel DuPage团队近期取得重要工作进展，他们研究发现，调节性T细胞中CXCR3的表达驱动与肿瘤中I型树突状细胞相互作用从而限制CD8⁺ T细胞的抗肿瘤免疫。相关研究成果2023年6月30日在线发表于《免疫》杂志上。

据介绍，调节性T（Treg）细胞（CD4⁺ T细胞的一种免疫抑制群体）渗入实体癌是癌症免疫治疗的一个障碍。趋化因子受体对于包括癌症在内的炎症组织中的Treg细胞募集和细胞间相互作用至关重要，可以作为一个理想的治疗靶点。

研究人员在多个癌症模型中发现，与淋巴组织相比，肿瘤中的CXCR3⁺ Treg细胞增多，表现出活化的表型，并优先与产生CXCL9的BATF3⁺树突状细胞（DC）相互作用。Treg细胞中CXCR3的基因消融破坏了DC1-Treg细胞的相互作用，并同时增加了DC-CD8⁺ T细胞的相互影响。从机制上讲，Treg细胞中的CXCR3消融增加了DC1s的肿瘤抗原特异性交叉呈递，增加了肿瘤中CD8⁺ T细胞的启动和再激活。这将最终损害肿瘤的进展，尤其是与抗PD-1检查点阻断免疫疗法联合使用。

总之，CXCR3被证明是肿瘤中Treg细胞积聚和免疫抑制的关键趋化因子受体。

附：英文原文

Title: CXCR3 expression in regulatory T cells drives interactions with type I dendritic cells in tumors to restrict CD8+ T cell antitumor immunity

Author: Mariela A. Moreno Ayala, Timothy F. Campbell, Chenyu Zhang, Noa Dahan, Alissa Bockman, Varsha Prakash, Lawrence Feng, Theo Sher, Michel DuPage

Issue&Volume: 2023-06-30

Abstract: Infiltration of regulatory T (Treg) cells, an immunosuppressive population of CD4+ T cells, into solid cancers represents a barrier to cancer immunotherapy. Chemokinereceptors are critical for Treg cell recruitment and cell-cell interactions in inflamedtissues, including cancer, and thus are an ideal therapeutic target. Here, we showin multiple cancer models that CXCR3+ Treg cells were increased in tumors compared with lymphoid tissues, exhibited anactivated phenotype, and interacted preferentially with CXCL9-producing BATF3+ dendritic cells (DCs). Genetic ablation of CXCR3 in Treg cells disrupted DC1-Tregcell interactions and concomitantly increased DC-CD8+ T cell interactions. Mechanistically, CXCR3 ablation in Treg cells increased tumorantigen-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 andimmune suppression in tumors.

DOI: 10.1016/j.immuni.2023.06.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00260-1

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