Piva Roberto, Gharari Nariman, Labrador Maria, Mader Sylvie
Department of Molecular Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy.
Città della Salute e della Scienza Hospital, 10126 Turin, Italy.
Cancers (Basel). 2024 Sep 26;16(19):3280. doi: 10.3390/cancers16193280.
The metabolic reprogramming characteristic of cancer cells, including the Warburg effect, has long been recognized as a hallmark of malignancy. This commentary explores three recent investigations focusing on the role of wild-type IDH2 in cancer and immune cell function. The first publication identifies wild-type IDH2 as a crucial factor in the survival of triple-negative breast cancer (TNBC) cells, with its inhibition leading to disrupted energy metabolism, reduced tumor growth, and enhanced apoptosis. The second analysis examines the role of IDH2 in CD8+ T cells, revealing that its inhibition promotes the differentiation of memory T cells, thereby enhancing the efficacy of cell-based immunotherapies like CAR T cells. A third investigation supports these findings, demonstrating that IDH2 inhibition in CAR T cells reduces exhaustion, enhances memory T cell formation, and improves anti-tumor efficacy. Collectively, these reports highlight wild-type IDH2 as a promising therapeutic target, with potential applications as a two-edged sword in both cancer treatment and immunotherapy. The development of specific wild-type IDH2 inhibitors could offer new avenues for therapy, particularly in tumors reliant on IDH2 activity as well as in enhancing the effectiveness of CAR T cell therapies.
癌细胞的代谢重编程特征，包括瓦伯格效应，长期以来一直被视为恶性肿瘤的标志。这篇评论探讨了三项最近的研究，这些研究聚焦于野生型异柠檬酸脱氢酶2（IDH2）在癌症和免疫细胞功能中的作用。第一篇发表的文章将野生型IDH2确定为三阴性乳腺癌（TNBC）细胞存活的关键因素，抑制它会导致能量代谢紊乱、肿瘤生长减缓以及细胞凋亡增加。第二项分析研究了IDH2在CD8 + T细胞中的作用，发现抑制它可促进记忆T细胞的分化，从而提高基于细胞的免疫疗法（如嵌合抗原受体T细胞疗法）的疗效。第三项研究支持了这些发现，表明在嵌合抗原受体T细胞中抑制IDH2可减少耗竭、增强记忆T细胞形成并提高抗肿瘤疗效。总体而言，这些报告突出了野生型IDH2作为一个有前景的治疗靶点，在癌症治疗和免疫疗法中都有作为双刃剑的潜在应用。特异性野生型IDH2抑制剂的开发可为治疗提供新途径，特别是在依赖IDH2活性的肿瘤中，以及在增强嵌合抗原受体T细胞疗法的有效性方面。
