Lyu Meng-Yuan, Lai Hong-Li, Peng Hao-Ran, Luo Han, Zhou Jian, Ma Wan-An-Qi, Zhang Chun-Ying, Ruan Hong-Xia, Liu Yang, Chen Jie, Ying Bin-Wu
Department of Laboratory Medicine/Clinical Laboratory Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
Sichuan Clinical Research Center for Laboratory Medicine, Chengdu, 610041, China.
Mil Med Res. 2025 Oct 20;12(1):68. doi: 10.1186/s40779-025-00655-7.
The worldwide dissemination of drug-resistant tuberculosis (TB) presents significant obstacles to conventional anti-TB treatment and prevention methods based on bactericidal antimicrobial drugs, greatly impeding advancements in combating this most lethal disease. With growing insights into the immunopathogenesis of TB, we are increasingly recognizing the potential of immunotherapeutic strategies aimed at targeting the host. After invading the host, Mycobacterium tuberculosis (M. tuberculosis) induces host cell exhaustion through its own molecules, such as early secretory antigen target-6 (ESAT-6) and di-O-acyl-trehalose, manifested as suppressed proliferative capacity, cytokine production, and cytotoxicity, thereby triggering the onset of TB. In response to this pathogenic mechanism, immunotherapeutic strategies, including cell therapy and immune checkpoint inhibitors, have been developed to promote cytokine production, activate immune cells to exhibit anti-TB activities such as autophagy, and restore immune homeostasis, including the balance between T helper 1 (Th1) and Th2 responses. These approaches have shown promise in restoring host immunity and demonstrating therapeutic effects against TB. However, a comprehensive evaluation of factors such as drug safety, optimal treatment duration, and others, is essential before these strategies can be integrated into routine clinical TB management. The advancement of immunotherapy has the potential to revolutionize current TB management and provide further benefits to patients. This review aims to comprehensively explore the advancements in diverse TB immunotherapeutic strategies, including efficacy, safety, and administration methods, and to explore the challenges and prospects of TB immunotherapy.
耐多药结核病在全球范围内的传播给基于杀菌抗菌药物的传统抗结核治疗和预防方法带来了重大障碍，极大地阻碍了抗击这种最致命疾病的进展。随着对结核病免疫发病机制的深入了解，我们越来越认识到针对宿主的免疫治疗策略的潜力。结核分枝杆菌侵入宿主后，通过其自身分子，如早期分泌抗原靶标6（ESAT-6）和二-O-酰基海藻糖，诱导宿主细胞耗竭，表现为增殖能力、细胞因子产生和细胞毒性受到抑制，从而引发结核病。针对这一致病机制，已开发出包括细胞疗法和免疫检查点抑制剂在内的免疫治疗策略，以促进细胞因子产生，激活免疫细胞表现出如自噬等抗结核活性，并恢复免疫稳态，包括辅助性T细胞1（Th1）和Th2反应之间的平衡。这些方法在恢复宿主免疫力和显示抗结核治疗效果方面已显示出前景。然而，在将这些策略纳入常规临床结核病管理之前，对药物安全性、最佳治疗持续时间等因素进行全面评估至关重要。免疫治疗的进展有可能彻底改变当前的结核病管理，并为患者带来更多益处。本综述旨在全面探讨各种结核病免疫治疗策略的进展，包括疗效、安全性和给药方法，并探讨结核病免疫治疗的挑战和前景。
