Exosomes released from PD-L1+ tumor associated macrophages promote peritoneal metastasis of epithelial ovarian cancer by up-regulating T cell lipid metabolism

Epithelial ovarian cancer (EOC) tends to metastasize to the peritoneum, and the prognosis of patients is poor. In the peritoneum of patients with EOC, TAMs (tumor associated macrophages) regulate the imbalance of T cell ratio and promote the progression and metastasis of EOC. However, the mechanism...

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Bibliographic Details
Published in:	Biochemistry and biophysics reports Vol. 36; p. 101542
Main Authors:	Ma, Jun, Cen, Qianqian, Wang, Qingzhu, Liu, Li, Zhou, Jieru
Format:	Journal Article
Language:	English
Published:	Elsevier B.V 01-12-2023 Elsevier
Subjects:	CD8+ T cells Epithelial ovarian cancer PD-L1 Peritoneal metastasis Tumor associated macrophages PD-L1 Peritoneal metastasis Tumor associated macrophages CD8+ T cells Epithelial ovarian cancer
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Summary:	Epithelial ovarian cancer (EOC) tends to metastasize to the peritoneum, and the prognosis of patients is poor. In the peritoneum of patients with EOC, TAMs (tumor associated macrophages) regulate the imbalance of T cell ratio and promote the progression and metastasis of EOC. However, the mechanism of peritoneal metastasis in EOC patients remains unclear. Here, we confirmed that the percentages of PD-L1+ TAMs in EOC tissues increased significantly, and TAMs-derived PD-L1+ exosomes affected the transcription factor PPARα to up-regulate the expression of CPT1A in CD8+ T cells, promote fatty acid oxidation, and increase reactive oxygen species to cause cell damage. The apoptosis of CD8+ T cells was increased, and the expressions of their exhaustion markers LAG3, TIM-3, and PD-1 were also up-regulated. TAMs affect T cell function through lipid metabolism, leading to peritoneal immune imbalance and promoting peritoneal metastasis of EOC. This study reveals the mechanism by which TAMs in the peritoneal microenvironment regulate T cell lipid metabolism through exosome delivery of PD-L1, and the effect of lipid metabolism on T cell function, reveals the molecular mechanism of tumor immune microenvironment affecting EOC metastasis, and further explores related pathways whether molecular blockade can be used as a means to intervene in disease progression is expected to establish a new strategy for the diagnosis and treatment of EOC. •We showed PD-L1+ TAMs exosomes influence the effector function of CD8+ T cell.•We firstly discovered the mechanism that PD-L1+ TAMs exosomes promote CD8+ T cell exhaustion and the lipid metabolism through PPARα.•Furthermore, single-cell RNA sequencing data showed that CPT1A was highly expressed on T cells in EOC.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2405-5808 2405-5808
DOI:	10.1016/j.bbrep.2023.101542