研究动态
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CAF-免疫细胞相互作用及其对免疫疗法的影响。

CAF-immune cell crosstalk and its impact in immunotherapy.

发表日期:2022 Dec 08
作者: Ana Maia, Anna Schöllhorn, Juliane Schuhmacher, Cécile Gouttefangeas
来源: Seminars in Immunopathology

摘要:

肿瘤细胞并不存在孤立的实体,相反,它们被各种细胞和细胞外基质包围,形成肿瘤微环境(TME)。越来越多的证据表明,癌细胞与其微环境之间的相互作用在决定患者预后方面至关重要。TME包括环绕肿瘤细胞的一切,通常被后者控制以促进其生长、侵袭和免疫逃逸。免疫细胞和癌相关成纤维细胞(CAFs)是TME的重要组成部分,越来越多的证据表明它们的相互作用不仅在肿瘤进展中发挥了重要作用,而且在治疗反应中也是关键因素。免疫肿瘤学领域的最新研究产生了旨在激活免疫细胞反对癌细胞以消除它们的新疗法。尽管它们取得了前所未有的成功,但大部分患者没有反应的现象仍然存在,这凸显了进一步进展和改进的必要性。为了实现其最终目标,必须深入研究癌细胞与TME之间的相互作用,以允许针对抵抗或难治性机制的靶向研究。此外,缺乏预测性和预后性生物标志物进行患者分层。在本文中,我们着重探讨TME中复杂的CAFs及其如何与免疫细胞相互作用会导致治疗失败。我们进一步讨论了如何进一步剖析这种交流,以及目前用于针对它们的策略。©2022.作者(们)。
Tumour cells do not exist as isolated entities. Instead, they are surrounded by a variety of cells and extracellular matrix, which form the tumour microenvironment (TME). The interaction between cancer cells and their microenvironment is increasingly acknowledged as essential in dictating the outcome of the patients. The TME includes everything that surrounds tumour cells and is often highjacked by the latter to promote their growth, invasion, and immune escape. Immune cells and cancer-associated fibroblasts (CAFs) are essential components of the TME, and there is increasing evidence that their interaction constitutes a major player not only for tumour progression but also for therapy response.Recent work in the field of immuno-oncology resulted in the development of novel therapies that aim at activating immune cells against cancer cells to eliminate them. Despite their unprecedented success, the lack of response from a large portion of patients highlights the need for further progress and improvement. To achieve its ultimate goal, the interaction between cancer cells and the TME needs to be studied in-depth to allow the targeting of mechanisms that are involved in resistance or refractoriness to therapy. Moreover, predictive and prognostic biomarkers for patient stratification are still missing. In this review, we focus on and highlight the complexity of CAFs within the TME and how their interaction, particularly with immune cells, can contribute to treatment failure. We further discuss how this crosstalk can be further dissected and which strategies are currently used to target them.© 2022. The Author(s).