中国医学科学院张连军研究小组在研究中取得进展。他们揭示了琥珀酸盐保持CD8⁺ T细胞适应性，增强抗肿瘤免疫。相关论文于2025年8月14日发表于国际顶尖学术期刊《免疫学》杂志上。

该团队发现琥珀酸盐在缺乏SDH亚单位B （SDHB）的肿瘤中的积累增强了肿瘤反应性CD8⁺ T细胞介导的免疫反应。持续的琥珀酸暴露促进了CD8⁺ T细胞的存活，促进了茎样亚群的产生和维持。机制上，琥珀酸盐通过Bcl-2/腺病毒E1B 19 kDa相互作用蛋白3 （BNIP3）介导的线粒体自噬增强线粒体适应性，并通过表观遗传调节促进干细胞相关基因的表达。琥珀酸条件CD8⁺ T细胞表现出优越的长期持久性和肿瘤控制能力。

此外，琥珀酸富集特征与某些接受免疫检查点阻断治疗的黑色素瘤和胃癌患者的良好临床结果相关。这些发现揭示了琥珀酸盐如何保持T细胞的干细胞性，并强调了琥珀酸盐补充剂在增强T细胞免疫治疗效果方面的治疗潜力。

研究人员表示，琥珀酸是一种三羧酸循环中间体，在琥珀酸脱氢酶（SDH）突变的肿瘤中积累。虽然琥珀酸盐被认为可以调节CD8⁺ T细胞的细胞毒性，但其对T细胞分化的影响仍然知之甚少。

附：英文原文

Title: Succinate preserves CD8+ T cell fitness to augment antitumor immunity

Author: Kaili Ma, Hongcheng Cheng, Lin Wang, Han Xiao, Fenghua Liu, Yu Yang, Zhen Xiao, Kun Tang, Shicheng Li, Gang Wang, Minmin Ge, Jiajia Wang, Xiaowei Liu, Hai-Xi Sun, Ziyi Luo, Zhimin Gu, Ping-Chih Ho, Guideng Li, Lianjun Zhang

Issue&Volume: 2025-08-14

Abstract: Succinate, a tricarboxylic acid cycle intermediate, accumulates in tumors with succinate dehydrogenase (SDH) mutations. Although succinate is recognized for modulating CD8+ T cell cytotoxicity, its impact on T cell differentiation remains poorly understood. Here, we reveal that succinate accumulation in tumors lacking the SDH subunit B (SDHB) enhanced tumor-reactive CD8+ T cell-mediated immune responses. Sustained succinate exposure promoted CD8+ T cell survival and facilitated the generation and maintenance of stem-like subpopulations. Mechanistically, succinate enhanced mitochondrial fitness through Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)-mediated mitophagy and also promoted stemness-associated gene expression via epigenetic modulation. Succinate-conditioned CD8+ T cells displayed superior long-term persistence and tumor control capacity. Moreover, succinate enrichment signature correlates with favorable clinical outcomes in certain melanoma and gastric cancer patients receiving immune checkpoint blockade therapy. These findings reveal how succinate preserves T cell stemness and highlight the therapeutic potential of succinate supplementation for enhancing T cell immunotherapy efficacy.

DOI: 10.1016/j.immuni.2025.07.017

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00326-7