肿瘤细胞治疗研究
英文原题：CXCR3 signaling promotes Delta One T cell recruitment and antitumor efficacy in colorectal cancer.
CXCR3 signaling promotes Delta One T cell recruitment and antitumor efficacy in colorectal cancer.
免疫治疗已经改变了癌症治疗格局，但其在实体瘤、尤其是结直肠癌（CRC）中的疗效仍受限于内源性或过继转移免疫细胞浸润不足。
免疫治疗已经改变了癌症治疗格局，但其在实体瘤、尤其是结直肠癌（CRC）中的疗效仍受限于内源性或过继转移免疫细胞浸润不足。我们团队开发了Delta One T（DOT）细胞，这是一种异体Vδ1富集型γδ T细胞产品，已在CRC模型中显示出疗效，但引导其肿瘤归巢的关键机制尚不清楚。在这里，我们发现DOT细胞在扩增过程中获得了一种特定的趋化因子受体谱以支持肿瘤浸润，其特征是CXCR3的显著表达。重要的是，CXCR3配体（CXCL9-11）由CRC细胞系和原发肿瘤表达，并与Vδ1 T细胞浸润和DOT细胞募集相关。CXCR3信号对于DOT细胞在体外和体内的迁移至关重要，因为药理学阻断减少了肿瘤归巢，而增强CXCR3配体表达则增加了DOT细胞浸润并改善了肿瘤控制。这些发现确立了CXCR3信号是DOT细胞运输的关键调节因子，也是增强基于γδ T细胞的CRC免疫治疗的一个主要靶点。
Immunotherapy has transformed cancer treatment, yet its efficacy in solid tumors, and particularly in colorectal cancer (CRC), remains limited by insufficient infiltration of endogenous or adoptively transferred immune cells. Our group developed Delta One T (DOT) cells, an allogeneic Vδ1-enriched γδ T-cell product with demonstrated efficacy in CRC models, but the critical mechanisms guiding their tumor homing are unclear. Here we show that DOT cells acquire a specific chemokine receptor profile during expansion to support tumor infiltration, characterized by prominent CXCR3 expression. Importantly, CXCR3 ligands (CXCL9-11) are expressed by CRC cell lines and primary tumors, and correlate with Vδ1 T cell infiltration and DOT-cell recruitment. CXCR3 signaling is critical for DOT-cell migration in vitro and in vivo, as pharmacologic blockade reduced tumor homing, whereas enhancing CXCR3 ligand expression increased DOT-cell infiltration and improved tumor control. These findings establish CXCR3 signaling as a key regulator of DOT-cell trafficking and a prime target to boost γδ T cell-based immunotherapies for CRC.
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