Pseudomonas aeruginosa PcrV Enhances the Nitric Oxide-Mediated Tumoricidal Activity of Tumor-Associated Macrophages via a TLR4/PI3K/AKT/mTOR-Glycolysis-Nitric Oxide Circuit

Tumor-associated macrophages (TAMs), which display a tumor-supportive M2 phenotype, are closely related to tumor growth and metastasis. The reprogramming of TAMs toward a tumoricidal M1 profile has emerged as an attractive strategy for cancer immunotherapy. In this study, we found that the intratumo...

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Autores principales:	Hua Yu, Ying Bai, Jing Qiu, Xiaomei He, Junzhi Xiong, Qian Dai, Xingmin Wang, Yuanyuan Li, Halei Sheng, Rong Xin, Lu Jiang, Qiaoqiao Li, Defeng Li, Hong Zhang, Le Zhang, Qian Chen, Jin Peng, Xiaomei Hu, Kebin Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Pseudomonas aeruginosa PcrV protein TAM reeducation tumoricidal efficacy TLR4/PI3K/AKT/mTOR-glycolysis-NO feedback loop PcrV–TLR4 interaction Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/3b6f24f61d9f48d5acc98567f852e72c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

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spelling	oai:doaj.org-article:3b6f24f61d9f48d5acc98567f852e72c2021-11-30T20:53:35ZPseudomonas aeruginosa PcrV Enhances the Nitric Oxide-Mediated Tumoricidal Activity of Tumor-Associated Macrophages via a TLR4/PI3K/AKT/mTOR-Glycolysis-Nitric Oxide Circuit2234-943X10.3389/fonc.2021.736882https://doaj.org/article/3b6f24f61d9f48d5acc98567f852e72c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.736882/fullhttps://doaj.org/toc/2234-943XTumor-associated macrophages (TAMs), which display a tumor-supportive M2 phenotype, are closely related to tumor growth and metastasis. The reprogramming of TAMs toward a tumoricidal M1 profile has emerged as an attractive strategy for cancer immunotherapy. In this study, we found that the intratumoral injection of PcrV protein, a component of the Pseudomonas aeruginosa type 3 secretion system, suppressed tumor growth and increased apoptosis, inducible nitric oxide synthase (iNOS) expression, and the percentage of M1-polarized TAMs in tumor tissues. Furthermore, the intratumoral injection of PcrV-primed macrophages exerted a similar tumoricidal effect. In vitro analyses revealed that PcrV reeducated TAMs toward an antitumoral M1 phenotype and augmented their nitric oxide (NO)-mediated cytotoxicity against cancer cells. Mechanistically, we found that these effects were dependent on the activation of Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)-mediated regulation of a PI3K/AKT/mTOR-glycolysis-NO feedback loop via direct interaction with TLR4. Collectively, these results revealed a potential role for PcrV in cancer immunotherapy through the targeting of TAM plasticity.Hua YuYing BaiJing QiuXiaomei HeJunzhi XiongQian DaiXingmin WangYuanyuan LiHalei ShengRong XinLu JiangQiaoqiao LiDefeng LiHong ZhangLe ZhangQian ChenJin PengXiaomei HuKebin ZhangFrontiers Media S.A.articlePseudomonas aeruginosa PcrV proteinTAM reeducationtumoricidal efficacyTLR4/PI3K/AKT/mTOR-glycolysis-NO feedback loopPcrV–TLR4 interactionNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Pseudomonas aeruginosa PcrV protein TAM reeducation tumoricidal efficacy TLR4/PI3K/AKT/mTOR-glycolysis-NO feedback loop PcrV–TLR4 interaction Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Pseudomonas aeruginosa PcrV protein TAM reeducation tumoricidal efficacy TLR4/PI3K/AKT/mTOR-glycolysis-NO feedback loop PcrV–TLR4 interaction Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Hua Yu Ying Bai Jing Qiu Xiaomei He Junzhi Xiong Qian Dai Xingmin Wang Yuanyuan Li Halei Sheng Rong Xin Lu Jiang Qiaoqiao Li Defeng Li Hong Zhang Le Zhang Qian Chen Jin Peng Xiaomei Hu Kebin Zhang Pseudomonas aeruginosa PcrV Enhances the Nitric Oxide-Mediated Tumoricidal Activity of Tumor-Associated Macrophages via a TLR4/PI3K/AKT/mTOR-Glycolysis-Nitric Oxide Circuit
description	Tumor-associated macrophages (TAMs), which display a tumor-supportive M2 phenotype, are closely related to tumor growth and metastasis. The reprogramming of TAMs toward a tumoricidal M1 profile has emerged as an attractive strategy for cancer immunotherapy. In this study, we found that the intratumoral injection of PcrV protein, a component of the Pseudomonas aeruginosa type 3 secretion system, suppressed tumor growth and increased apoptosis, inducible nitric oxide synthase (iNOS) expression, and the percentage of M1-polarized TAMs in tumor tissues. Furthermore, the intratumoral injection of PcrV-primed macrophages exerted a similar tumoricidal effect. In vitro analyses revealed that PcrV reeducated TAMs toward an antitumoral M1 phenotype and augmented their nitric oxide (NO)-mediated cytotoxicity against cancer cells. Mechanistically, we found that these effects were dependent on the activation of Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)-mediated regulation of a PI3K/AKT/mTOR-glycolysis-NO feedback loop via direct interaction with TLR4. Collectively, these results revealed a potential role for PcrV in cancer immunotherapy through the targeting of TAM plasticity.
format	article
author	Hua Yu Ying Bai Jing Qiu Xiaomei He Junzhi Xiong Qian Dai Xingmin Wang Yuanyuan Li Halei Sheng Rong Xin Lu Jiang Qiaoqiao Li Defeng Li Hong Zhang Le Zhang Qian Chen Jin Peng Xiaomei Hu Kebin Zhang
author_facet	Hua Yu Ying Bai Jing Qiu Xiaomei He Junzhi Xiong Qian Dai Xingmin Wang Yuanyuan Li Halei Sheng Rong Xin Lu Jiang Qiaoqiao Li Defeng Li Hong Zhang Le Zhang Qian Chen Jin Peng Xiaomei Hu Kebin Zhang
author_sort	Hua Yu
title	Pseudomonas aeruginosa PcrV Enhances the Nitric Oxide-Mediated Tumoricidal Activity of Tumor-Associated Macrophages via a TLR4/PI3K/AKT/mTOR-Glycolysis-Nitric Oxide Circuit
title_short	Pseudomonas aeruginosa PcrV Enhances the Nitric Oxide-Mediated Tumoricidal Activity of Tumor-Associated Macrophages via a TLR4/PI3K/AKT/mTOR-Glycolysis-Nitric Oxide Circuit
title_full	Pseudomonas aeruginosa PcrV Enhances the Nitric Oxide-Mediated Tumoricidal Activity of Tumor-Associated Macrophages via a TLR4/PI3K/AKT/mTOR-Glycolysis-Nitric Oxide Circuit
title_fullStr	Pseudomonas aeruginosa PcrV Enhances the Nitric Oxide-Mediated Tumoricidal Activity of Tumor-Associated Macrophages via a TLR4/PI3K/AKT/mTOR-Glycolysis-Nitric Oxide Circuit
title_full_unstemmed	Pseudomonas aeruginosa PcrV Enhances the Nitric Oxide-Mediated Tumoricidal Activity of Tumor-Associated Macrophages via a TLR4/PI3K/AKT/mTOR-Glycolysis-Nitric Oxide Circuit
title_sort	pseudomonas aeruginosa pcrv enhances the nitric oxide-mediated tumoricidal activity of tumor-associated macrophages via a tlr4/pi3k/akt/mtor-glycolysis-nitric oxide circuit
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3b6f24f61d9f48d5acc98567f852e72c
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Pseudomonas aeruginosa PcrV Enhances the Nitric Oxide-Mediated Tumoricidal Activity of Tumor-Associated Macrophages via a TLR4/PI3K/AKT/mTOR-Glycolysis-Nitric Oxide Circuit

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