From granulomas to tumors: post-tuberculosis immune and structural lung remodeling as a driver of carcinogenesis.

Although antibiotic therapy effectively cures active tuberculosis (TB), many survivors are left with permanent lung damage and long-lasting immune alterations. Growing epidemiological evidence indicates that individuals with prior pulmonary TB have a two- to three-fold increased risk of lung cancer, independent of smoking, suggesting mechanisms beyond shared risk factors. This review advances the concept that TB imprints a durable "memory" within the lung, characterized by persistent structural remodeling and immune reprogramming that together create a tumor-permissive microenvironment. We synthesize evidence showing that TB granulomas act as dynamic immune niches that induce hypoxia, fibrosis, and immune exhaustion, features that frequently persist after microbiological cure. Post-TB sequelae including fibrotic scarring, cavitation, bronchiectasis, and vascular remodeling, promote chronic inflammation, oxidative DNA damage, and mechanotransduction pathways linked to oncogenesis. Concurrently, sustained T-cell exhaustion, macrophage polarization toward tumor-associated phenotypes, and impaired antigen presentation weaken tumor surveillance. We further discuss emerging roles for lung microbiome dysbiosis in sustaining inflammation. Collectively, these processes provide a mechanistic framework linking healed TB to lung carcinogenesis and highlight TB survivors as a distinct population for targeted surveillance and preventive strategies.