Zhang Yv-Yin, He Jia-Jun, Liu Yi-Lin, Shao Ruo-Nan, Bai Kun-Hao, Li Xue-Ping, Guo Tao, Wang Pei-Hong, Dai Yu-Jun
Department of Hematology, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
NPJ Precis Oncol. 2025 May 15;9(1):142. doi: 10.1038/s41698-025-00933-6.
Immune checkpoint blockade (ICB) therapy has emerged as a pivotal advancement in cancer treatment, yet its efficacy varies among patients and resistance can develop. This study focuses on TIGIT, a newly identified immune checkpoint, to explore its expression, prognostic significance, and therapeutic potential in hematologic malignancies, particularly acute myeloid leukemia (AML). In this study, we found TIGIT highest expression levels in bone marrow and lymphoid tissues, with enrichment in immune cells such as NK-T cells and regulatory T cells (Tregs). A prognostic model incorporating TIGIT expression and other immune-related genes effectively stratified AML patients into high-risk and low-risk groups, with the former displaying significantly shorter overall survival times. Our model outperformed traditional prognostic factors, highlighting TIGIT's potential as a superior predictive biomarker. Additionally, our in vitro and in vivo studies showed that combining tiragolumab with azacitidine (AZA) synergistically enhanced anti-tumor efficacy, reducing tumor burden and extending survival in a murine AML model. Our findings underscore TIGIT's role in hematologic malignancies and its potential as a therapeutic target in AML. The combination of AZA with TIGIT inhibition offers a promising new approach for AML treatment, warranting further clinical evaluation.
免疫检查点阻断（ICB）疗法已成为癌症治疗中的一项关键进展，但其疗效因患者而异，且可能产生耐药性。本研究聚焦于新发现的免疫检查点TIGIT，以探索其在血液系统恶性肿瘤，尤其是急性髓系白血病（AML）中的表达、预后意义及治疗潜力。在本研究中，我们发现TIGIT在骨髓和淋巴组织中表达水平最高，在NK-T细胞和调节性T细胞（Tregs）等免疫细胞中富集。一个纳入TIGIT表达及其他免疫相关基因的预后模型有效地将AML患者分为高危和低危组，前者的总生存时间显著缩短。我们的模型优于传统预后因素，凸显了TIGIT作为一种更优预测生物标志物的潜力。此外，我们的体外和体内研究表明，在小鼠AML模型中，将替雷利珠单抗与阿扎胞苷（AZA）联合使用可协同增强抗肿瘤疗效，减轻肿瘤负担并延长生存期。我们的研究结果强调了TIGIT在血液系统恶性肿瘤中的作用及其作为AML治疗靶点的潜力。AZA与TIGIT抑制联合使用为AML治疗提供了一种有前景的新方法，值得进一步的临床评估。
