Department of Clinical Medicine, University of Bergen, Bergen, Norway.
Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Ups J Med Sci. 2024 May 24;129. doi: 10.48101/ujms.v126.10710. eCollection 2024.
Cancer-associated fibroblasts (CAFs) are a heterogeneous cell population recognized as a key component of the tumour microenvironment (TME). Cancer-associated fibroblasts are known to play an important role in maintaining and remodelling the extracellular matrix (ECM) in the tumour stroma, supporting cancer progression and inhibiting the immune system's response against cancer cells. This review aims to summarize the immunomodulatory roles of CAFs, particularly focussing on their T-cell suppressive effects. Cancer-associated fibroblasts have several ways by which they can affect the tumour's immune microenvironment (TIME). For example, their interactions with macrophages and dendritic cells (DCs) create an immunosuppressive milieu that can indirectly affect T-cell anticancer immunity and enable immune evasion. In addition, a number of recent studies have confirmed CAF-mediated direct suppressive effects on T-cell anticancer capacity through ECM remodelling, promoting the expression of immune checkpoints, cytokine secretion and the release of extracellular vesicles. The consequential impact of CAFs on T-cell function is then reflected in affecting T-cell proliferation and apoptosis, migration and infiltration, differentiation and exhaustion. Emerging evidence highlights the existence of specific CAF subsets with distinct capabilities to modulate the immune landscape of TME in various cancers, suggesting the possibility of their exploitation as possible prognostic biomarkers and therapeutic targets.
癌症相关成纤维细胞(CAFs)是一种异质性细胞群体,被认为是肿瘤微环境(TME)的关键组成部分。已知癌症相关成纤维细胞在维持和重塑肿瘤基质中的细胞外基质(ECM)方面发挥重要作用,支持癌症进展并抑制免疫系统对癌细胞的反应。本综述旨在总结 CAFs 的免疫调节作用,特别是重点关注它们对 T 细胞的抑制作用。CAFs 可以通过多种方式影响肿瘤的免疫微环境(TIME)。例如,它们与巨噬细胞和树突状细胞(DCs)的相互作用形成了一种免疫抑制环境,可间接影响 T 细胞抗肿瘤免疫并实现免疫逃逸。此外,一些最近的研究证实了 CAF 通过 ECM 重塑对 T 细胞抗肿瘤能力的直接抑制作用,促进免疫检查点的表达、细胞因子的分泌和细胞外囊泡的释放。CAFs 对 T 细胞功能的影响随后反映在影响 T 细胞的增殖和凋亡、迁移和浸润、分化和耗竭上。新出现的证据强调了存在具有不同能力的特定 CAF 亚群,可调节各种癌症中 TME 的免疫景观,表明有可能将其作为可能的预后生物标志物和治疗靶点加以利用。
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