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针对三阴性乳腺癌中肿瘤细胞与肿瘤相关巨噬细胞之间的分子串扰作为治疗策略。

Targeting molecular cross-talk between tumor cells and tumor associated macrophage as therapeutic strategy in triple negative breast cancer.

机构信息

Department of Molecular and Cellular Biology, National Institute for Research in Reproductive and Child Health, Mumbai, India.

Department of Molecular and Cellular Biology, National Institute for Research in Reproductive and Child Health, Mumbai, India.

出版信息

Int Immunopharmacol. 2023 Jun;119:110250. doi: 10.1016/j.intimp.2023.110250. Epub 2023 May 8.

Abstract

Triple-negative Breast cancer (TNBC) is a subtype of breast cancer (BC) that lacks expression for ER/PR/Her2 receptors and is associated with aggressive disease pathogenesis and the worst prognosis among other subtypes of BC. Accumulating evidence-based studies indicate the high immunogenic ability of TNBC tumors and the applicability of immunotherapeutic strategies to overcome therapy resistance and tumor recurrence in TNBC patients. However, not all TNBC patients respond equally well to current immunotherapies that mainly target the adaptive immune system for tumor rejection. Recent studies are contemplating the efficacy of tumor-associated macrophage (TAM) targeted therapies since these subpopulations of cells comprise one of the major components of tumor-infiltrating immune cells (TIIs) in the TNBC tumor microenvironment (TME) and play an essential role in priming the adaptive immune response mediators towards both antitumorigenic and pro-tumorigenic response facilitated by intercellular cross-talk between tumor cells and TAM populations present within TNBC-TME. The present review discusses these molecular mechanisms and their consequence on the progression of TNBC tumors. Also, the therapeutic strategies targeting candidate genes/pathways involved in molecular cross-talk between TAM-TNBC cells and their impact on the development and progression of TNBC tumors are also discussed.

摘要

三阴性乳腺癌(TNBC)是一种缺乏 ER/PR/Her2 受体表达的乳腺癌(BC)亚型,与侵袭性疾病发病机制和其他 BC 亚型中最差的预后相关。越来越多的基于证据的研究表明,TNBC 肿瘤具有高度的免疫原性能力,并且免疫治疗策略适用于克服 TNBC 患者的治疗耐药性和肿瘤复发。然而,并非所有 TNBC 患者对目前主要针对适应性免疫系统以排斥肿瘤的免疫疗法都有同样的反应。最近的研究正在考虑针对肿瘤相关巨噬细胞(TAM)的靶向治疗的疗效,因为这些细胞亚群是 TNBC 肿瘤微环境(TME)中浸润肿瘤免疫细胞(TII)的主要成分之一,并且在通过肿瘤细胞和 TNBC-TME 中存在的 TAM 群体之间的细胞间相互作用促进适应性免疫反应介导物向抗肿瘤和促肿瘤反应方面发挥着重要作用。本综述讨论了这些分子机制及其对 TNBC 肿瘤进展的影响。此外,还讨论了针对 TAM-TNBC 细胞之间分子相互作用涉及的候选基因/途径的治疗策略及其对 TNBC 肿瘤发生和进展的影响。

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