Immunotherapy for tuberculosis: current strategies and future directions

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.