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用于挖掘M1肿瘤相关巨噬细胞(TAM)对实体瘤治疗潜力的新型新辅助剂:可塑性的利用

Emerging neo adjuvants for harnessing therapeutic potential of M1 tumor associated macrophages (TAM) against solid tumors: Enusage of plasticity.

作者信息

Nadella Vinod, Garg Manoj, Kapoor Sonia, Barwal Tuhar Singh, Jain Aklank, Prakash Hridayesh

机构信息

Laboratory of Translational Medicine, School of Life Sciences, University of Hyderabad, Telangana, India.

Amity Institute of Molecular Medicine and Stem cell Research, Amity University Uttar Pradesh, Sector 125, Noida, India.

出版信息

Ann Transl Med. 2020 Aug;8(16):1029. doi: 10.21037/atm-20-695.

Abstract

Macrophages are a major component of the tumor microenvironment (TME) of most tumors. They are characterized by a high degree of functional plasticity which enable these cells to both promote and eliminate established tumors. Under the influence of immunosuppressive TME, tumor infiltrating iNOS+ and CD11b+ M-1 effector macrophages get polarized towards tumor associated macrophages (TAM) which are tropic to variety of tumors. Increased infiltration and density of TAM is associated with tumor progression and poor prognosis in the plethora of tumors due to their angiogenetic and tissue re-modelling nature. Importantly, TAMs are also responsible for developing endothelium anergy, a major physical barrier for majority of cancer directed immune/chemotherapies. Therefore, functional retuning/re-educating TAM to M-1 phenotypic macrophages is paramount for effective immunotherapy against established tumors. In this review, we discuss and provide comprehensive update on TAM-targeted approaches for enhancing immunity against various solid tumors.

摘要

巨噬细胞是大多数肿瘤的肿瘤微环境(TME)的主要组成部分。它们的特点是具有高度的功能可塑性,这使得这些细胞既能促进已形成的肿瘤生长,也能消除肿瘤。在免疫抑制性肿瘤微环境的影响下,肿瘤浸润的诱导型一氧化氮合酶(iNOS)阳性和CD11b阳性M-1效应巨噬细胞会向肿瘤相关巨噬细胞(TAM)极化,TAM对多种肿瘤具有嗜性。由于TAM具有血管生成和组织重塑的特性,其浸润增加和密度升高与多种肿瘤的进展及不良预后相关。重要的是,TAM还会导致内皮细胞无反应性,这是大多数针对癌症的免疫/化疗的主要物理障碍。因此,将TAM功能重新调整/再教育为M-1表型巨噬细胞对于针对已形成肿瘤的有效免疫治疗至关重要。在本综述中,我们讨论并全面更新了针对TAM的方法,以增强对各种实体瘤的免疫力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/939e/7475467/7fa9d2704011/atm-08-16-1029-f1.jpg

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