Integrated Single-Cell Analysis Reveals the Heterogeneity of Tumor-Associated Macrophages and Their Implications for Immunotherapy in Colorectal Cancer.

Background: Tumor-associated macrophages (TAMs) are one of the predominant cell components within the colorectal cancer (CRC) microenvironment, which display prominent and multifaceted roles in modulating tumor biology. The systematic subtypes and function analysis of TAMs remain elusive in CRC. Methods: We performed an integrated single-cell atlas of three American studies (GSE178341, GSE200997, and GSE231559) to establish the TAM subtypes in the CRC microenvironment. We adopted unsupervised clustering and manual cell annotation to categorize macrophage subtypes accurately, performed enrichment analysis and developmental trajectory analysis for three TAM subsets, and explored the cell-to-cell crosstalk of different TAM subsets with other cell types. Finally, we further performed an integrated single-cell atlas of five Asian studies (GSE132257, GSE132465, GSE144735, GSE221575, and GSE245552) to validate these characteristics of different TAM subtypes. Results: We identified three TAM subtypes, including CCL20 Conclusion: This single-cell study established an accurate classification system of CRC TAMs, unveiling their diverse roles in modulating tumor biology and assisting in treatment options of CRC patients.