Given one-third of the world’s population is infected with Mycobacteriumtuberculosis (MTB), it is important to identify the underling molecular mechanism between development of TB and lung cancer. This study investigated the immune response to MTB infection on lung metastasis in lung cancer cells via T cell-mediated immune response. To clarify this problem, we analyzed the expression levels of PD-1, PD-L1, and PD-L2 and immune function in antigen-specific T cell as derived from MTB patients or spleen lymphocytes derived from wild-type and PD-1 knockout mice with MTB antigen stimulation and Lewis lung cancer cells injection. Our data indicate that the expression levels of PD-1, PD-L1, and PD-L2 were elevated in active pulmonary TB patients, as well as in mice received MTB and lung cancer cells treatment. We also observed the T cell-mediated cellular immune response were inhibited by MTB while MTB significantly promote tumor metastasis in lung. In conclusion, the PD-1/PD-L pathway is required MTB repressed T-cell immune response and promotes tumor metastasis. This study provides evidence that blockade of PD-1/PD-L1 signaling pathway may benefit patients with MTB or other chronic infection and even prevent them from development of cancer.

Background: The present study aimed to investigate the association of CD45RO⁺, CD8⁺, CCR7⁺ and FOXP3⁺ tumor-infiltrating lymphocytes (TILs) with the clinicopathological features as well as survival of patients with lung adenocarcinoma. Methods: Ninety patients with lung adenocarcinoma who underwent surgery were recruited in the present study. Lung adenocarcinoma tissues and paired adjacent lung tissues were obtained from all participants, and immunohistochemistry was performed to detect the expression of CD45RO, CD8, CCR7 and FOXP3. After multiplying the staining intensity score by the labeling frequency score, the immunohistochemical results were divided into three groups: TILs low, TILs intermediate and TILs high. Results: CD45RO⁺, CD8⁺ and CCR7⁺ infiltrating lymphocytes were markedly increased in lung adenocarcinoma (all P<0.001) while FOXP3⁺ infiltrating lymphocytes were reduced (P<0.001) compared with than in adjacent tissues. CD45RO⁺ TILs were negatively associated with tumor size (P=0.002), lymph node metastasis (P<0.001) and TNM stage (P<0.001). CD8⁺ TILs were also negatively correlated with lymph node metastasis (P=0.016). Kaplan-Meier curve analysis revealed that CD45RO⁺ TILs were positively associated with longer disease-free survival (DFS) (P<0.001) and overall survival (OS) (P<0.001). Univariate and multivariate Cox’s proportional hazards regression confirmed that CD45RO⁺ TILs (high) independently predicted longer DFS (P=0.002) and OS (P=0.009). Conclusions: The present study demonstrates that CD45RO⁺ TILs are negatively correlated with tumor size, lymph node metastasis and TNM stage and that CD45RO⁺ TILs (high) can be regarded as a novel and promising biomarker for prolonged DFS and OS in lung adenocarcinoma patients.