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

BACKGROUND: 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...

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Autores principales: Adah, Dickson, Yang, Yijun, Liu, Quan, Gadidasu, Kranthi, Tao, Zhu, Yu, Songlin, Dai, Linglin, Li, Xiaofen, Zhao, Siting, Qin, Limei, Qin, Li, Chen, Xiaoping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461823/
https://www.ncbi.nlm.nih.gov/pubmed/30979375
http://dx.doi.org/10.1186/s12964-019-0342-6
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author Adah, Dickson
Yang, Yijun
Liu, Quan
Gadidasu, Kranthi
Tao, Zhu
Yu, Songlin
Dai, Linglin
Li, Xiaofen
Zhao, Siting
Qin, Limei
Qin, Li
Chen, Xiaoping
author_facet Adah, Dickson
Yang, Yijun
Liu, Quan
Gadidasu, Kranthi
Tao, Zhu
Yu, Songlin
Dai, Linglin
Li, Xiaofen
Zhao, Siting
Qin, Limei
Qin, Li
Chen, Xiaoping
author_sort Adah, Dickson
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12964-019-0342-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-64618232019-04-22 Plasmodium infection inhibits the expansion and activation of MDSCs and Tregs in the tumor microenvironment in a murine Lewis lung cancer model Adah, Dickson Yang, Yijun Liu, Quan Gadidasu, Kranthi Tao, Zhu Yu, Songlin Dai, Linglin Li, Xiaofen Zhao, Siting Qin, Limei Qin, Li Chen, Xiaoping Cell Commun Signal Research BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12964-019-0342-6) contains supplementary material, which is available to authorized users. BioMed Central 2019-04-12 /pmc/articles/PMC6461823/ /pubmed/30979375 http://dx.doi.org/10.1186/s12964-019-0342-6 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Adah, Dickson
Yang, Yijun
Liu, Quan
Gadidasu, Kranthi
Tao, Zhu
Yu, Songlin
Dai, Linglin
Li, Xiaofen
Zhao, Siting
Qin, Limei
Qin, Li
Chen, Xiaoping
Plasmodium infection inhibits the expansion and activation of MDSCs and Tregs in the tumor microenvironment in a murine Lewis lung cancer model
title Plasmodium infection inhibits the expansion and activation of MDSCs and Tregs in the tumor microenvironment in a murine Lewis lung cancer model
title_full Plasmodium infection inhibits the expansion and activation of MDSCs and Tregs in the tumor microenvironment in a murine Lewis lung cancer model
title_fullStr Plasmodium infection inhibits the expansion and activation of MDSCs and Tregs in the tumor microenvironment in a murine Lewis lung cancer model
title_full_unstemmed Plasmodium infection inhibits the expansion and activation of MDSCs and Tregs in the tumor microenvironment in a murine Lewis lung cancer model
title_short Plasmodium infection inhibits the expansion and activation of MDSCs and Tregs in the tumor microenvironment in a murine Lewis lung cancer model
title_sort plasmodium infection inhibits the expansion and activation of mdscs and tregs in the tumor microenvironment in a murine lewis lung cancer model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6461823/
https://www.ncbi.nlm.nih.gov/pubmed/30979375
http://dx.doi.org/10.1186/s12964-019-0342-6
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