mouse glioma tissue sc-RNA sequencing

With the deepening understanding of cancer, the roles of psychological factors, especially chronic stress-induced depression, in the occurrence and development of tumors have drawn increasing amounts of attention. However, whether and how depression affects the progression of gliomas are still unclear. In this study, we revealed, for the first time, that chronic stress inhibited the recruitment of tumor-associated macrophages (TAMs) and other immune cells, especially M1-type TAMs and CD8+ T cells, and decreased the level of proinflammatory cytokines in gliomas, leading to an immunosuppressive microenvironment and glioma progression. Mechanistically, by promoting the secretion of stress hormones, chronic stress inhibited the secretion of the chemokine CCL3 and the recruitment of M1-type TAMs in gliomas. Supplementation of CCL3 reprogrammed the immuno-microenvironment of gliomas and abolished the progression of gliomas induced by chronic stress. Importantly, CCL3 and M1-type TAMs decreased in the tumor tissues of glioma patients with depression, and CCL3 supplementation enhanced the antitumor effect of anti-PD-1 therapy in orthotopic gliomas undergoing chronic stress. In conclusion, our study revealed that chronic stress exacerbates the immunosuppressive microenvironment and progression of gliomas by reducing the secretion of CCL3. CCL3 alone or in combination with an anti-PD-1 antibody may be an effective immunotherapy for the treatment of gliomas with depression.