Pseudomonas aeruginosa PcrV Enhances the Nitric Oxide-Mediated Tumoricidal Activity of Tumor-Associated Macrophages via a TLR4/PI3K/AKT/mTOR-Glycolysis-Nitric Oxide Circuit.
Pseudomonas aeruginosa PcrV Enhances the Nitric Oxide-Mediated Tumoricidal Activity of Tumor-Associated Macrophages via a TLR4/PI3K/AKT/mTOR-Glycolysis-Nitric Oxide Circuit.
复制标题
铜绿假单胞菌 PcrV 通过 TLR4/PI3K/AKT/mTOR-糖酵解-一氧化氮回路增强肿瘤相关巨噬细胞的一氧化氮介导的杀肿瘤活性
DOI：
10.3389/fonc.2021.736882
复制
发表时间：
2021
影响因子：
4.7
通讯作者：
Zhang K
中科院分区：
文献类型：
--
作者：
Yu H;Bai Y;Qiu J;He X;Xiong J;Dai Q;Wang X;Li Y;Sheng H;Xin R;Jiang L;Li Q;Li D;Zhang H;Zhang L;Chen Q;Peng J;Hu X;Zhang K
肿瘤相关巨噬细胞（TAM）具有肿瘤支持性M2表型，与肿瘤生长和转移密切相关。将 TAM 重编程为杀肿瘤 M1 谱已成为癌症免疫治疗的一种有吸引力的策略。在这项研究中，我们发现肿瘤内注射PcrV蛋白（铜绿假单胞菌3型分泌系统的一个组成部分）可以抑制肿瘤生长并增加细胞凋亡、诱导型一氧化氮合酶（iNOS）表达以及肿瘤组织中M1极化TAM的百分比。此外，瘤内注射 PcrV 引发的巨噬细胞也发挥了类似的杀肿瘤作用。体外分析表明，PcrV 将 TAM 重新训练为抗肿瘤 M1 表型，并增强了其一氧化氮 (NO) 介导的针对癌细胞的细胞毒性。从机制上讲，我们发现这些作用依赖于 Toll 样受体 4 (TLR4)/骨髓分化因子 88 (MyD88) 的激活，通过与 TLR4 的直接相互作用介导 PI3K/AKT/mTOR-糖酵解-NO 反馈环路的调节。总的来说，这些结果揭示了 PcrV 通过靶向 TAM 可塑性在癌症免疫治疗中的潜在作用。
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.
登录
查看更多内容
影响因子：
4.3
作者：
Bolanos, Juan P.;Delgado-Esteban, Maria;Almeida, Angeles
通讯作者：
Almeida, Angeles
黄精多糖通过TLR4-MAPK/NF-kappa B信号通路发挥抗癌作用
DOI：
10.1016/j.ijbiomac.2018.01.070
发表时间：
2018-05-01
影响因子：
8.2
作者：
Long, Tingting;Liu, Zijing;Bao, Yixi
通讯作者：
Bao, Yixi
影响因子：
4.8
作者：
Karar J;Maity A
通讯作者：
Maity A
影响因子：
5.6
作者：
Chen CY;Kao CL;Liu CM
通讯作者：
Liu CM
影响因子：
4.6
作者：
Kim J;Bae JS
通讯作者：
Bae JS