Integrative single-cell sequencing analysis distinguishes survival-associated cells from the breast cancer microenvironment

Abstract

Background: Breast cancer shows a highly complex tumor microenvironment by containing various cell types. Identifying prognostic cell populations in the tumor microenvironment will improve the mechanistical understanding of breast cancer and facilitate the development of new breast cancer therapies by targeting the tumor microenvironment. The development of single-cell sequencing reveals various cell types, states, and lineages within the context of heterogenous breast tumors, but identifying phenotype-associated subpopulations is challenging.

Results: Here, we applied Scissor (single-cell identification of subpopulations with bulk Sample phenotype correlation) to integrate single cell and bulk data of breast cancer, and found that MHC-deficient tumor cells, FABP5+ macrophages, and COL1A1+ cancer-associated fibroblasts (CAFs) were detrimental to patient survival, while T cells and dendritic cells were the main protective cells. MHC-deficient tumor cells show strong downregulation of MHC expression for immune evasion by downregulating interferon and JAK-STATs signaling. FABP5+ macrophages show low antigen-presenting activity via associating with lipid metabolism. Our data suggest that COL1A1+ CAFs may block T-cell immune infiltration through cell interaction in breast tumor microenvironment.

Conclusion: Taken together, our study reveals survival-associated subpopulations in breast tumor microenvironment. Importantly, subpopulations related to immune evasion of breast cancer is uncovered.

Keywords: breast cancer; immune evasion; prognostic cell; single-cell sequencing; tumor microenvironment.