The intricate tumor microenvironment presents formidable obstacles to the efficacy of adoptive T cell therapy in the management of solid tumors by limiting the infiltration and inducing exhaustion of the transferred T cells. Here, we developed a bacterial-based adjuvant approach that augments the efficacy of adoptive T-cell therapy for solid tumor treatment. Our study reveals that intratumor injection of E. coli MG1655 normalizes tumor vasculatures and reprograms tumor-associated macrophages into M1 phenotype that produce abundant CCL5, together facilitating tumor infiltration of adoptively transferred T cells. The depletion of tumor-associated macrophages or CCL5 neutralization in vivo leads to the significantly decreased solid tumor infiltration of adoptive T cells in the presence of bacteriotherapy. This combinatorial therapy, consisting of E. coli adjuvant and adoptive T-cell therapy, effectively eradicates early-stage melanoma and inhibits the progression of pancreatic tumors. Notably, this dual strategy also strengthened the distal tumor control capabilities of adoptive T-cell therapy through the induction of in situ tumor vaccination. This dual therapeutic approach involving bacterial therapy targeting the interior of solid tumors and adoptive T-cell therapy attacking the tumor periphery exhibits potent therapeutic efficacy in achieving the eradication of advanced-stage tumors, including melanoma and hepatocellular carcinoma, by converging attacks from both inside and outside the tumor tissues.

错综复杂的肿瘤微环境通过限制转移的 T 细胞的浸润和诱导耗竭，为过继 T 细胞疗法在实体瘤治疗中的疗效带来了巨大的障碍。在这里，我们开发了一种基于细菌的辅助方法，可增强过继性 T 细胞疗法对实体瘤治疗的疗效。我们的研究表明，肿瘤内注射大肠杆菌 MG1655 使肿瘤脉管系统正常化，并将肿瘤相关巨噬细胞重编程为 M1 表型，从而产生丰富的 CCL5，共同促进过继转移 T 细胞的肿瘤浸润。在细菌疗法存在下，体内肿瘤相关巨噬细胞的耗竭或 CCL5 中和导致过继性 T 细胞的实体瘤浸润显着减少。这种组合疗法由大肠杆菌辅助和过继性 T 细胞疗法组成，可有效根除早期黑色素瘤并抑制胰腺肿瘤的进展。值得注意的是，这种双重策略还通过诱导原位肿瘤疫苗接种加强了过继性 T 细胞疗法的远端肿瘤控制能力。这种双重治疗方法包括针对实体瘤内部的细菌疗法和攻击肿瘤外周的过继性 T 细胞疗法，通过汇聚来自肿瘤组织内部和外部的攻击，在实现根除晚期肿瘤（包括黑色素瘤和肝细胞癌）方面表现出强大的治疗效果。