Single-cell advances in stromal-leukocyte interactions in cancer

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.