Abstract:
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.
摘要:
探索和利用肺结核(TB)肉芽肿和恶性肿瘤之间的微环境相似性揭示了更有效的宿主导向疗法(HDT)的新策略。这篇观点文章讨论了结核病治疗发展的范式转变,借鉴肿瘤学的重要见解。我们总结了最近的努力来表征和克服肿瘤和肉芽肿之间的关键共同特征。包括过度的纤维化,血管生成异常,缺氧和坏死,和免疫抑制。我们提供了癌症治疗应用于结核病的具体例子,以克服这些微环境异常,包括基质靶向治疗,抗血管生成剂,和免疫刺激药物。最后,我们提出了一个新的框架,将HDT与抗结核药物相结合,以最大限度地提高治疗效果和疗效,同时减少治疗剂量。持续时间,和有害的副作用使结核病患者受益。