The full potential of tumor-infiltrating lymphocyte (TIL) therapy has been hampered by the inadequate activation and low persistence of TILs, as well as inefficient neoantigen presentation by tumors. We transformed tumor cells into artificial antigen-presenting cells (aAPCs) by infecting them with a herpes simplex virus 1 (HSV-1)-based oncolytic virus encoding OX40L and IL12 (OV-OX40L/IL12) to provide local signals for optimum T cell activation. The infected tumor cells displayed increased expression of antigen-presenting cell-related markers and induced enhanced T cell activation and killing in coculture with TILs. Combining OV-OX40L/IL12 and TIL therapy induced complete tumor regression in patient-derived xenograft and syngeneic mouse tumor models and elicited an antitumor immunological memory. In addition, the combination therapy produced aAPC properties in tumor cells, activated T cells, and reprogrammed macrophages to a more M1-like phenotype in the tumor microenvironment. This combination strategy unleashes the full potential of TIL therapy and warrants further evaluation in clinical studies.

肿瘤浸润淋巴细胞 (TIL) 治疗的全部潜力受到 TIL 激活不足和低持久性以及肿瘤新抗原呈递效率低下的阻碍。我们通过用编码 OX40L 和 IL12 (OV-OX40L/IL12) 的基于单纯疱疹病毒 1 (HSV-1) 的溶瘤病毒 (OV-OX40L/IL12) 感染它们来将肿瘤细胞转化为人工抗原呈递细胞 (aAPC)，从而为最佳 T 细胞提供局部信号激活。受感染的肿瘤细胞表现出抗原呈递细胞相关标记物的表达增加，并在与 TIL 的共培养中诱导增强的 T 细胞活化和杀伤。结合 OV-OX40L/IL12 和 TIL 疗法在患者来源的异种移植和同源小鼠肿瘤模型中诱导完全肿瘤消退，并引发抗肿瘤免疫记忆。此外，联合疗法在肿瘤细胞中产生 aAPC 特性，激活 T 细胞，并将巨噬细胞重新编程为肿瘤微环境中更像 M1 的表型。这种组合策略释放了 TIL 治疗的全部潜力，并需要在临床研究中进行进一步评估。