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Abstract. Lung cancer is the most common malignancy in humans. An increased population of CD4 + Foxp3 + regulatory T cells (Tregs) in the tumor-associated microenvironment plays an important role in cancer immune evasion. The exact role and the involved mechanisms of concomitant H37Rv infection in non-small cell lung cancer (NSCLC) development are still not clear. Here, we showed that H37Rv infection promoted NSCLC cell growth with a higher percentage of Tregs found in draining lymph nodes. We also determined in vitro that H37Rv infection induced macrophage maturation and PD-L1 expression, which promoted Treg proportion, with enhanced proliferation suppression function. Mechanism analysis revealed that AKT-mTORC1 signal was important for PD-L1 expression induced by H37Rv infection. Suppressing of AKT-mTORC1 signal by rapamycin or raptor deficiency showed decreased PD-L1 levels which further reduced Treg proportion in a co-culture system. Finally, tumor-bearing mice injected with H37Rv plus rapamycin enhance the immune response of lung cancer compared with injected with H37Rv alone. This study demonstrated that concomitant H37Rv infection promote NSCLC tumor immune eacape through enhancing Treg proportion. IntroductionLung cancer is one of the most common malignancies with severe mortality worldwide (1,2). There are ermerging treatments for lung cancer including surgery, irradiation, chemotherapy and immunotherapy. However, prognosis remains unsatisfactory (3-5). Recently, comorbid cancer-infection which represents an independent concomitant microorganism infection in tumor has attracted new attention, since certain microorganism infection might induce antitumor immunity responses for a new treatment strategy. Malaria infection significantly suppresses murine Lewis lung cancer growth via induction of innate and adaptive antitumor responses in a mouse model, suggesting that the malaria parasite may stand for a new strategy or therapeutic vaccine vector for anti-lung cancer immunotherapy (6). T. gondii infection inhibits tumor growth in the Lewis lung carcinoma mouse model through the induction of Th1 immune responses and anti-angiogenic activity (7).Mycobacterium tuberculosis (MTB) is an obligate pathogenic bacterial species in the family Mycobacteriaceae and the causative agent of tuberculosis (8). Mononuclear cells recruited to sites of MTB infection or novel MTB antigens, are exposed to MTB Toll-like receptor (TLR) ligands. MTB is rich in TLR2 ligands (9,10), and a role for TLR2 ligand in expansion of Treg has been previously shown (11). MTB and its components expand functional CD4 + Foxp3 + Treg, which implicates for effective immunization against MTB (12,13). It was also reported that active tuberculosis in non-small cell lung cancer (NSCLC) patients shows better survival outcome, possibly due to the T lymphocyte infiltration in tumors (14). However, the role of an independent H37Rv infection in the development of NSCLC is not quite clear.Here, we demonstrated that independent MTB H37Rv infection facilitated ...