Depression Promotes Cancer Growth

Release date:2019-03-22  Release:主页英文版

Recently, Professor YANG Yong's team at Institute of Pharmaceutical Sciences of China Pharmaceutical University published their latest research finding in the academic journal Clinical Cancer Research (IF 10.199) “Depression induced neuropeptide Y secretion promotes prostate cancer growth by recruiting myeloid cells” (pp.clincanres-2912). This research clarifies the new regulatory mechanism of depression involved in shaping the immune microenvironment of prostate cancer and accelerating the progression of prostate cancer. China Pharmaceutical University is the first author’s institution, Professor YANG Yong is the corresponding author, CHENG Hao, TANG Xinying and LI Yizhen are the first authors.

        In recent years, studies have shown that the nervous system plays an important role in regulating tumor immunity, but the exact mechanism remains unclear. In this project, Professor YANG's team focused on the regulation of immune cells in the tumor microenvironment by depression, in order to explain the shaping of the tumor microenvironment by mental stress.

        The researchers inoculated homologous Myc-CaP prostate cancer cells in immunocompromised FVB mice and constructed a mouse depression model with chronic unpredictable mild stress. Studies have shown that the tumor growth of the stress group is significantly accelerated, and the spectrum of immune cells in the tumor microenvironment changes, and the proportion and number of mononuclear-MDSC are significantly increased. A similar phenomenon was also found in Hi-myc mice with spontaneous prostate cancer. Further exploration revealed that the increased MDSC in the tumor microenvironment is derived from the spleen and peripheral blood of mice, and MDSC can differentiate into tumor-associated macrophages (TAMs) to promote tumor development after entering the tumor microenvironment.

        After RNA Seq analysis, the researchers found neuropeptide Y (NPY), a key molecule in the recruitment of depression and MDSC. Norepinephrine activates tumor cell β2AR and promotes NPY production. NPY not only recruits macrophages, but also promotes the secretion of IL-6, activates the STAT3 pathway of tumor cells, and promotes tumor development. The researchers further validated the above findings in clinical patient samples and found that patients with higher levels of depression had significantly increased macrophage infiltration in tumor tissues, and the expression of NPY and IL-6 was also strongly positive. The above studies have shown that blocking the β2AR-NPY signal axis can help to improve the inhibitory tumor immune microenvironment, and can be used as a new treatment for prostate patients with high degree of depression.

The CCR journal board invited the famous neuroimmunologist Elizabeth A. Repasky for peer review (pp.clincanres-3980), arguing that the study clarified a new mechanism for depression-promoting tumor growth, and that blocking adrenergic signal or NPY signal pathway may become a new strategy for tumor immunotherapy.

Translated from

Written by TANG Xinying, Institute of Pharmaceutical Sciences of China Pharmaceutical University