The transcription factors nuclear factor of activated T cells (NFAT) and activator protein 1 (AP-1; Fos–Jun) cooperate to promote the effector functions of T cells, but NFAT in the absence of AP-1 imposes a negative feedback program of T cell hyporesponsiveness (exhaustion). Here, we show that basic leucine zipper ATF-like transcription factor (BATF) and interferon regulatory factor 4 (IRF4) cooperate to counter T cell exhaustion in mouse tumor models. Overexpression of BATF in CD8⁺ T cells expressing a chimeric antigen receptor (CAR) promoted the survival and expansion of tumor-infiltrating CAR T cells, increased the production of effector cytokines, decreased the expression of inhibitory receptors and the exhaustion-associated transcription factor TOX and supported the generation of long-lived memory T cells that controlled tumor recurrence. These responses were dependent on BATF–IRF interaction, since cells expressing a BATF variant unable to interact with IRF4 did not survive in tumors and did not effectively delay tumor growth. BATF may improve the antitumor responses of CAR T cells by skewing their phenotypes and transcriptional profiles away from exhaustion and towards increased effector function.

活化 T 细胞 (NFAT) 和激活蛋白 1 (AP-1; Fos–Jun) 的转录因子核因子协同促进 T 细胞的效应功能，但在没有 AP-1 的情况下，NFAT 会施加一个负反馈程序T 细胞反应性低下（衰竭）。在这里，我们表明碱性亮氨酸拉链 ATF 样转录因子 (BATF) 和干扰素调节因子 4 (IRF4) 协同对抗小鼠肿瘤模型中的 T 细胞衰竭。^{CD8 +}中 BATF 的过表达表达嵌合抗原受体 (CAR) 的 T 细胞促进肿瘤浸润性 CAR T 细胞的存活和扩增，增加效应细胞因子的产生，降低抑制性受体和耗竭相关转录因子 TOX 的表达，并支持长链的产生- 控制肿瘤复发的存活记忆 T 细胞。这些反应依赖于 BATF-IRF 相互作用，因为表达 BATF 变体的细胞无法与 IRF4 相互作用，无法在肿瘤中存活，也无法有效延缓肿瘤生长。BATF 可以通过使 CAR T 细胞的表型和转录谱从耗竭状态转向增加的效应功能来改善 CAR T 细胞的抗肿瘤反应。