Plasmodium infection inhibits the expansion and activation of MDSCs and Tregs in the tumor microenvironment in a murine Lewis lung cancer model

• Published in: Cell communication and signaling Vol. 17; no. 1; p. 32
• Main Authors: Adah, Dickson, Yang, Yijun, Liu, Quan, Gadidasu, Kranthi, Tao, Zhu, Yu, Songlin, Dai, Linglin, Li, Xiaofen, Zhao, Siting, Qin, Limei, Qin, Li, Chen, Xiaoping
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12-04-2019; BioMed Central; BMC
• Subjects: Animals; Antigens; Arginase; Bone marrow; Cancer therapies; Carcinoma, Lewis Lung - immunology; Carcinoma, Lewis Lung - therapy; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell growth; Cell Line, Tumor; Cytokines; Cytotoxicity, Immunologic; Development and progression; Erythrocytes; Female; Genetic aspects; Genotype & phenotype; Granzymes - immunology; Immunosuppression - methods; Infections; Inflammation; Laboratory animals; Liver; Lung cancer; Lymphocytes; Lymphocytes T; Malaria; Malaria - immunology; MDSC; Medical prognosis; Merozoites; Metabolism; Mice; Mice, Inbred C57BL; Monocytes; Myeloid-Derived Suppressor Cells - immunology; Nitric-oxide synthase; PD-1; Physiological aspects; Plasmodium; Plasmodium yoelii - immunology; Pore Forming Cytotoxic Proteins - immunology; Programmed Cell Death 1 Receptor - immunology; Recruiting molecules; Sporozoites; Stat3 protein; Stem cells; T cells; T-Lymphocytes, Regulatory - immunology; Tregs; Tumor cells; Tumor Microenvironment - immunology; Tumors; China; United States > US; MDSC; Recruiting molecules; PD-1; Lung cancer; Tregs
• ISSN: 1478-811X; 1478-811X
• DOI: 10.1186/s12964-019-0342-6

A major challenge in the development of effective cancer immunotherapy is the ability of tumors and their microenvironment to suppress immune cells through immunosuppressive cells such as myeloid -derived suppressor cells and regulatory T cells. We previously demonstrated that Plasmodium infection promotes innate and adaptive immunity against cancer in a murine Lewis lung cancer model but its effects on immunosuppressive cells in the tumor microenvironment are unknown.
Whole Tumors and tumor-derived sorted cells from tumor-bearing mice treated with or without plasmodium infected red blood cells were harvested 17 days post tumor implantation and analyzed using QPCR, western blotting, flow cytometry, and functional assays. Differences between groups were analyzed for statistical significance using Student's t-test.
Here we found that Plasmodium infection significantly reduced the proportions of MDSCs and Tregs in the lung tumor tissues of the treated mice by downregulating their recruiting molecules and blocking cellular activation pathways. Importantly, CD8
T cells isolated from the tumors of Plasmodium-treated mice exhibited significantly higher levels of granzyme B and perforin and remarkably lower levels of PD-1.
We reveal for the first time, the effects of Plasmodium infection on the expansion and activation of MDSCs and Tregs with a consequent elevation of CD8
T cell-mediated cytotoxicity within the tumor microenvironment and hold great promise for the development of effective immunotherapeutic strategies.