过继细胞转移（ACT）是一种增强抗肿瘤免疫力的治疗策略。在此，我们报告用缺氧诱导因子 (HIF) 稳定剂二甲基乙二酰甘氨酸 (DMOG) 离体处理小鼠 CD8 T 细胞，诱导 HIF 与编码共刺激受体 CD81、GITR、OX40 和 4-1BB 的基因结合，导致表达量增加。 DMOG 治疗增加了 T 细胞对黑色素瘤细胞的杀伤力，针对每种共刺激受体的激动剂抗体进一步增强了这种杀伤力。在荷瘤小鼠中，与使用对照 T 细胞的 ACT 相比，使用经 DMOG 和激动剂抗体离体处理的 T 细胞进行的 ACT 导致肿瘤生长减少，并且 CD8 T 细胞（CD7、CD8A 和 CD8B1）、自然杀伤细胞的瘤内标记物增加（NCR1 和 KLRK1）和细胞溶解活性（穿孔素-1 和肿瘤坏死因子-α）。当用目前临床使用的三种高选择性 HIF 稳定剂处理 CD8 T 细胞时，也会诱导共刺激受体基因表达。

Adoptive cell transfer (ACT) is a therapeutic strategy to augment antitumor immunity. Here, we report that ex vivo treatment of mouse CD8+ T cells with dimethyloxalylglycine (DMOG), a stabilizer of hypoxia-inducible factors (HIFs), induced HIF binding to the genes encoding the costimulatory receptors CD81, GITR, OX40, and 4-1BB, leading to increased expression. DMOG treatment increased T cell killing of melanoma cells, which was further augmented by agonist antibodies targeting each costimulatory receptor. In tumor-bearing mice, ACT using T cells treated ex vivo with DMOG and agonist antibodies resulted in decreased tumor growth compared to ACT using control T cells and increased intratumoral markers of CD8+ T cells (CD7, CD8A, and CD8B1), natural killer cells (NCR1 and KLRK1), and cytolytic activity (perforin-1 and tumor necrosis factor-α). Costimulatory receptor gene expression was also induced when CD8+ T cells were treated with three highly selective HIF stabilizers that are currently in clinical use.