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肿瘤相关巨噬细胞与卵巢癌:对治疗的启示

Tumor-Associated Macrophages and Ovarian Cancer: Implications for Therapy.

作者信息

Schweer David, McAtee Annabel, Neupane Khaga, Richards Christopher, Ueland Frederick, Kolesar Jill

机构信息

Markey Cancer Center, Division of Gynecologic Oncology, University of Kentucky, Lexington, KY 40536, USA.

School of Medicine, University of Kentucky, Lexington, KY 40536, USA.

出版信息

Cancers (Basel). 2022 Apr 29;14(9):2220. doi: 10.3390/cancers14092220.

Abstract

The tumor microenvironment (TME) has been implicated to play an important role in the progression of ovarian cancer. One of the most important components of the TME is tumor associated macrophages (TAMs). Phenotypically, macrophages are broadly categorized as M1 pro-inflammatory or M2 anti-inflammatory, based on the cytokines and chemokines that they secrete. The tumor microenvironment is associated with macrophages of an M2 phenotype which suppress the surrounding immune environment, assist tumor cells in evading immune targeting, and support tumor growth and metastasis. Contrarily, M1 macrophages help mount an immune response against tumors, and are associated with a more favorable prognosis in solid tumors. One of the characteristic indicators of a poor prognosis in ovarian cancer is the overrepresentation of M2-type TAMs. As such, therapeutic modalities targeting TME and TAMs are of increasing interest. Pharmacological approaches to eliminate TAMs, include decreasing macrophage survival and recruitment and increasing phagocytosis, have been underwhelming. Clinical strategies targeting these macrophage subtypes via repolarization to an M1 antitumoral state deserve increasing attention, and may serve as a new modality for immunotherapy.

摘要

肿瘤微环境(TME)被认为在卵巢癌进展中起重要作用。肿瘤微环境的最重要组成部分之一是肿瘤相关巨噬细胞(TAM)。从表型上看,巨噬细胞根据其分泌的细胞因子和趋化因子大致分为促炎的M1型或抗炎的M2型。肿瘤微环境与M2表型的巨噬细胞相关,这些巨噬细胞会抑制周围的免疫环境,帮助肿瘤细胞逃避免疫靶向,并支持肿瘤生长和转移。相反,M1巨噬细胞有助于对肿瘤发起免疫反应,并且与实体瘤中更有利的预后相关。M2型肿瘤相关巨噬细胞比例过高是卵巢癌预后不良的特征性指标之一。因此,针对肿瘤微环境和肿瘤相关巨噬细胞的治疗方式越来越受到关注。消除肿瘤相关巨噬细胞的药理学方法,包括降低巨噬细胞存活率和募集率以及增强吞噬作用,效果并不理想。通过重新极化至M1抗肿瘤状态来靶向这些巨噬细胞亚型的临床策略值得更多关注,并且可能成为免疫治疗的一种新方式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1265/9101750/3abd23d5b26d/cancers-14-02220-g001.jpg

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