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Figure S6 from Chronic Stress Exacerbates the Immunosuppressive Microenvironment and Progression of Gliomas by Reducing Secretion of CCL3

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posted on 2024-05-02, 08:05 authored by Xu Wang, Long Zhang, Yi Zhou, Yan Wang, Xiang Wang, Yining Zhang, Ankang Quan, Yufei Mao, Yu Zhang, Ji Qi, Zhongyu Ren, Linbo Gu, Rutong Yu, Xiuping Zhou

Supplementary Figure 6. CCL3 treatment improves the migration of TAMs in vitro and the immune microenvironment of gliomas caused by chronic stress in vivo (Related to Fig.5)

Funding

National Natural Science Foundation of China (NSFC)

Natural Science Foundation of Jiangsu Province (Jiangsu Natural Science Foundation)

Jiangsu Provincial Key Research and Development Program (Key Technologies R&D Program of Jiangsu Province)

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ARTICLE ABSTRACT

As understanding of cancer has deepened, increasing attention has been turned to the roles of psychological factors, especially chronic stress–induced depression, in the occurrence and development of tumors. However, whether and how depression affects the progression of gliomas are still unclear. In this study, we have revealed that chronic stress inhibited the recruitment of tumor-associated macrophages (TAM) 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. Intratumoral administration of CCL3 reprogrammed the immune microenvironment of gliomas and abolished the progression of gliomas induced by chronic stress. Moreover, levels of CCL3 and M1-type TAMs were decreased in the tumor tissues of glioma patients with depression, and CCL3 administration enhanced the antitumor effect of anti–PD-1 therapy in orthotopic models of gliomas undergoing chronic stress. In conclusion, our study has 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 may be an effective immunotherapy for the treatment of gliomas with depression.See related Spotlight by Cui and Kang, p. 514.

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