Allam Amr, Yakou Marina, Pang Lokman, Ernst Matthias, Huynh Jennifer
Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, VIC, Australia.
Front Immunol. 2021 Nov 11;12:767939. doi: 10.3389/fimmu.2021.767939. eCollection 2021.
The tumor microenvironment (TME) is composed of a heterogenous population of cells that exist alongside the extracellular matrix and soluble components. These components can shape an environment that is conducive to tumor growth and metastatic spread. It is well-established that stromal cancer-associated fibroblasts (CAFs) in the TME play a pivotal role in creating and maintaining a growth-permissive environment for tumor cells. A growing body of work has uncovered that tumor cells recruit and educate CAFs to remodel the TME, however, the mechanisms by which this occurs remain incompletely understood. Recent studies suggest that the signal transducer and activator of transcription 3 (STAT3) is a key transcription factor that regulates the function of CAFs, and their crosstalk with tumor and immune cells within the TME. CAF-intrinsic STAT3 activity within the TME correlates with tumor progression, immune suppression and eventually the establishment of metastases. In this review, we will focus on the roles of STAT3 in regulating CAF function and their crosstalk with other cells constituting the TME and discuss the utility of targeting STAT3 within the TME for therapeutic benefit.
肿瘤微环境（TME）由与细胞外基质和可溶性成分共存的异质性细胞群体组成。这些成分可以塑造一个有利于肿瘤生长和转移扩散的环境。众所周知，TME中的基质癌相关成纤维细胞（CAF）在为肿瘤细胞创造和维持一个允许生长的环境中起着关键作用。越来越多的研究发现，肿瘤细胞招募并重塑CAF以改变TME，然而，其发生机制仍未完全明确。最近的研究表明，信号转导和转录激活因子3（STAT3）是一种关键的转录因子，可调节CAF的功能及其与TME内肿瘤细胞和免疫细胞的相互作用。TME内CAF自身的STAT3活性与肿瘤进展、免疫抑制以及最终转移的形成相关。在这篇综述中，我们将聚焦于STAT3在调节CAF功能及其与构成TME的其他细胞相互作用中的作用，并讨论在TME中靶向STAT3以获得治疗益处的实用性。
