Non-small cell lung cancer (NSCLC) is a major disease threatening human health, and the incidence and mortality rate are increasing year by year worldwide. 85% of NSCLC pathological classification belongs to lung adenocarcinoma. The advent of immune checkpoint inhibitors brings light to NSCLC therapy, and the antibody drug Pembrolizumab targeting PD-1 / PD-L1 is the first-line drug approved for the treatment of advanced and metastatic NSCLC. Although these agents have shown better efficacy in the treatment of metastatic or locally advanced NSCLC, only 15% – 30% of patients with advanced NSCLC can achieve sustained remission and long-term survival from immunotherapy, with a suppressive tumor immune microenvironment being its main cause. Therefore, it is very important to explore the drivers of inhibitory TIME formation to improve the efficacy of immunotherapy in NSCLC.
Endocrine hormones are closely related to tumor immunity. In some endocrine-related tumors (such as breast cancer, etc.), the involvement of hormones in tumor immune regulation has been deeply studied, and endocrine therapy has become an important means for the treatment of these tumors. NSCLC is not strictly endocrine-related tumors, but more and more studies show that the proliferation and metastasis of lung cancer cells is regulated by a variety of hormones, in the membrane surface has multiple hormone receptor, however, the medical community how endocrine hormones involved in NSCLC tumor immune microenvironment regulation, how to affect the NSCLC immune efficacy.
Recently, the research group of Professor Yin Wu from the School of Life Sciences of Nanjing University published in the Science subjournal Science Advances entitled: Na, And K-ATPase α1 cooperates with its endogenous ligand to reprogram immune microenvironment of lung carcinoma and promotes immune escape's research paper.
Professor Yin Wu's research group has been studying the new biological function of the endocrine hormone —— endogenous Endogenous Ouabain (EO) produced by the adrenal gland. Through a large number of clinical samples and biological function confirmation, they found that EO is a new endocrine hormone that can promote the inhibitory immune microenvironment of NSCLC.
Waabain is a chemical weapon produced by higher plants to resist insect invasion, but abnormally high expression of EO was detected in the blood of patients with non-small cell lung adenocarcinoma, and the amount of EO expression is closely related to tumor metastasis and patient prognosis. Further research found that in the progression of lung adenocarcinoma, the adrenal gland can be "hijacked" by tumor to release EO, and EO in the microenvironment of lung adenocarcinoma "skillfully" used sodium and potassium ATP enzyme receptor "desensitization" to accurately regulate PD-L1 expression and promote tumor immune escape. The novelty of the results was highly evaluated by international peer experts.
This study expands the new biological function of EO, and provides a theoretical basis for discovering a new mechanism of tumor immune escape and improving the effect of immunotherapy in lung adenocarcinoma.
