Abstract
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.
Highlights
Lung cancer is by far the leading cause of death from cancer, with an estimated 1.59 million people dying from lung cancer in 2016, accounting for approximately 20% of all cancer deaths worldwide[1]
We observed significantly increased expression levels of PD-1 (Fig. 1a, d), as well as its two ligands PD-L1 and PDL-2 (Fig. 1b, c, e, f) on CD3+ T cells from of pulmonary TB patients but not in control subjects
Our hypothesis was Mycobacterium tuberculosis (MTB) infection-mediated immune response and its facilitated tumor metastases is associated with PD-1/PD-L1 signaling pathway
Summary
Lung cancer is by far the leading cause of death from cancer, with an estimated 1.59 million people dying from lung cancer in 2016, accounting for approximately 20% of all cancer deaths worldwide[1]. The incidence and mortality of lung cancer have been increasing rapidly in China, making lung cancer the first leading cause of cancer death since 2010 and an emerging health issue in the country[2]. An up-to-date study of epidemiology of lung cancer in China, including smoking, air pollution, occupational risk factors, would provide the evidence base for Mycobacterium tuberculosis (MTB) is the pathogen that causes tuberculosis (TB), which is the world’s deadliest infectious diseases[4]. Most MTB infections do not have any symptoms and TB-induced inflammation often eventually lead to genetic change and even lung cancer. On the other hand, increased lung cancer incidence is related to immunosuppression status resulted from MTB infection[5,6]. Concurrent TB and lung cancer were reported in a large number of cases and case–control studies[7,8,9]
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