The efficacy of adoptive cell therapy for solid tumours is hampered by the poor accumulation of the transferred T cells in tumour tissue. Here, we show that forced expression of C-X-C chemokine receptor type 6 (whose ligand is highly expressed by human and murine pancreatic cancer cells and tumour-infiltrating immune cells) in antigen-specific T cells enhanced the recognition and lysis of pancreatic cancer cells and the efficacy of adoptive cell therapy for pancreatic cancer. In mice with subcutaneous pancreatic tumours treated with T cells with either a transgenic T-cell receptor or a murine chimeric antigen receptor targeting the tumour-associated antigen epithelial cell adhesion molecule, and in mice with orthotopic pancreatic tumours or patient-derived xenografts treated with T cells expressing a chimeric antigen receptor targeting mesothelin, the T cells exhibited enhanced intratumoral accumulation, exerted sustained anti-tumoral activity and prolonged animal survival only when co-expressing C-X-C chemokine receptor type 6. Arming tumour-specific T cells with tumour-specific chemokine receptors may represent a promising strategy for the realization of adoptive cell therapy for solid tumours.

实体瘤的过继细胞疗法的疗效因肿瘤组织中转移的 T 细胞积累不良而受到阻碍。在这里，我们发现，在抗原特异性T细胞中强制表达CXC趋化因子受体6型（其配体在人类和小鼠胰腺癌细胞以及肿瘤浸润免疫细胞中高度表达）增强了对胰腺癌细胞的识别和裂解，并且增强了胰腺癌细胞的识别和裂解能力。过继细胞疗法对胰腺癌的疗效。在用带有转基因 T 细胞受体或靶向肿瘤相关抗原上皮细胞粘附分子的鼠嵌合抗原受体的 T 细胞治疗的皮下胰腺肿瘤小鼠中，以及在用 T 治疗的原位胰腺肿瘤或患者来源的异种移植物的小鼠中表达针对间皮素的嵌合抗原受体的细胞，只有当共表达 CXC 趋化因子受体 6 型时，T 细胞才表现出增强的瘤内积累，发挥持续的抗肿瘤活性并延长动物存活时间。用肿瘤特异性趋化因子受体武装肿瘤特异性 T 细胞可能代表了实现实体瘤过继细胞治疗的一种有前景的策略。