Datta Meenal, Via Laura E, Dartois Véronique, Xu Lei, Barry Clifton E, Jain Rakesh K
Department of Aerospace and Mechanical Engineering, University of Notre Dame, Notre Dame, IN 46556, USA.
Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
Trends Mol Med. 2025 Jan;31(1):11-20. doi: 10.1016/j.molmed.2024.07.011. Epub 2024 Aug 13.
Exploring and exploiting the microenvironmental similarities between pulmonary tuberculosis (TB) granulomas and malignant tumors has revealed new strategies for more efficacious host-directed therapies (HDTs). This opinion article discusses a paradigm shift in TB therapeutic development, drawing on critical insights from oncology. We summarize recent efforts to characterize and overcome key shared features between tumors and granulomas, including excessive fibrosis, abnormal angiogenesis, hypoxia and necrosis, and immunosuppression. We provide specific examples of cancer therapy application to TB to overcome these microenvironmental abnormalities, including matrix-targeting therapies, antiangiogenic agents, and immune-stimulatory drugs. Finally, we propose a new framework for combining HDTs with anti-TB agents to maximize therapeutic delivery and efficacy while reducing treatment dosages, duration, and harmful side effects to benefit TB patients.
探索和利用肺结核（TB）肉芽肿与恶性肿瘤之间的微环境相似性，为更有效的宿主导向疗法（HDTs）揭示了新策略。这篇观点文章借鉴肿瘤学的关键见解，讨论了结核病治疗发展中的范式转变。我们总结了最近在表征和克服肿瘤与肉芽肿之间关键共同特征方面所做的努力，包括过度纤维化、异常血管生成、缺氧和坏死以及免疫抑制。我们提供了癌症治疗应用于结核病以克服这些微环境异常的具体例子，包括基质靶向疗法、抗血管生成药物和免疫刺激药物。最后，我们提出了一个将HDTs与抗结核药物相结合的新框架，以在减少治疗剂量、持续时间和有害副作用的同时，最大限度地提高治疗效果并使结核病患者受益。
