Wu Sunny Z, Swarbrick Alexander
The Kinghorn Cancer Centre and Cancer Research Theme, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
St Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia.
Immunol Rev. 2021 Jul;302(1):286-298. doi: 10.1111/imr.12976. Epub 2021 May 25.
Mesenchymal stromal cells in solid tumors have emerged as important mediators of immune function and response to immunotherapies. As such, comprehensive insights into their biology may reveal new predictors of drug response and new drug targets. While our understanding of mesenchymal biology in cancer is nascent, it is rapidly evolving, driven by advances in single-cell technologies. These studies reveal distinct subclasses of cancer-associated fibroblasts (CAFs) with unique properties for immune regulation and control of leukocyte activity. While these studies have revealed several similarities across distinct types of cancer, they still face key challenges in nomenclature. Single-cell analysis of tumors has also revealed an abundance of perivascular cells with unique biology and associations with immune infiltration. They are often misclassified, likely confounding previous bulk studies, revealing a distinct lineage of cells that remain to be fully characterized. These studies have also shed light on the discrete cell types or transient cell states that shape mesenchymal heterogeneity in tumors, offering insights into new therapeutic strategies to modulate stromal cell differentiation. In this review, we will address how recent advances in single-cell technologies have shaped our understanding of stromal heterogeneity and their coordination of immune responses in cancer.
实体瘤中的间充质基质细胞已成为免疫功能及免疫治疗反应的重要调节因子。因此，对其生物学特性的全面了解可能会揭示新的药物反应预测指标和新的药物靶点。尽管我们对癌症中间充质生物学的认识尚处于起步阶段，但在单细胞技术进步的推动下，这一领域正在迅速发展。这些研究揭示了癌症相关成纤维细胞（CAF）的不同亚类，它们具有免疫调节和控制白细胞活性的独特特性。虽然这些研究揭示了不同类型癌症之间的一些相似之处，但它们在命名方面仍面临关键挑战。对肿瘤的单细胞分析还揭示了大量具有独特生物学特性且与免疫浸润相关的血管周围细胞。它们常常被错误分类，这可能混淆了以往的整体研究，揭示出一个仍有待充分表征的独特细胞谱系。这些研究还揭示了塑造肿瘤中间充质异质性的离散细胞类型或瞬时细胞状态，为调节基质细胞分化的新治疗策略提供了见解。在这篇综述中，我们将探讨单细胞技术的最新进展如何塑造了我们对基质异质性及其在癌症中免疫反应协调作用的理解。
