Single-cell dissection of tumor microenvironmental response and resistance to cancer therapy.

Single-cell profiling technologies provide an unprecedented resolution in investigating the coordinated compositional and state alterations of immune and stromal components in response to cancer therapies on the tumor microenvironment, enabling a holistic and more nuanced understanding of treatment response and resistance. Multimodal characterization of the heterogeneity of baseline and perturbed adaptive immune populations, especially T cells, offers a foundation for the discovery of the most actionable therapeutic targets. Key players in the tumor microenvironment (TME) outside of the adaptive immune populations, including cancer-associated fibroblasts and macrophages, have emerged as effective mediators of cancer therapeutic response or resistance, frequently dependent on the crosstalk with T and B lymphocytes. Tumor-targeting treatments demonstrate widespread TME-modulating effects, often indirectly through consequent immunostimulating signaling elicited by remodeled tumor cells, justifying a combinatorial administration with immunotherapies. Cancer treatment strategies have evolved significantly over the years, with chemotherapy, targeted therapy, and immunotherapy as major pillars. Each modality leads to unique treatment outcomes by interacting with the tumor microenvironment (TME), which imposes a fundamental selective pressure on cancer progression. The advent of single-cell profiling technologies has revolutionized our understanding of the intricate and heterogeneous nature of the TME at an unprecedented resolution. This review delves into the commonalities and differential manifestations of how cancer therapies reshape the microenvironment in diverse cancer types. We highlight how groundbreaking immune checkpoint blockade (ICB) strategies alone or in combination with tumor-targeting treatments are endowed with comprehensive mechanistic insights when decoded at the single-cell level, aiming to drive forward future research directions on personalized treatments. [ABSTRACT FROM AUTHOR]