MGP+ and IDO1+ tumor-associated macrophages facilitate immunoresistance in breast cancer revealed by single-cell RNA sequencing

Abstract

Immunotherapy is widely applied for the treatment of breast cancer, but to which some patients respond poorly or develop resistance. Therefore, the mechanism needs to be further studied. Transcriptomic data of 31 breast cancer patients treated with anti-programmed death receptor 1 (PD-1) was downloaded from the VIB-KULeuven Center for Cancer Biology to analyze the changes in myeloid cells in tumor tissues before and after immunotherapy. And 24 cell populations that may be immune-related were further identified. Representative cell populations were also screened and validated through cellular and animal experiments to evaluate the relevant molecular expression and pathways of tumor-associated macrophages (TAMs) in the tumor microenvironment.The results demonstrated that MGP+ TAMs and IDO1+ TAMs influenced the efficacy of immunotherapy in breast cancer patients. After anti-PD-1 treatment, Increased numbers of MGP+ TAMs and IDO1+ TAMs in breast cancer patients upregulated pro-tumorigenic factors associated with resistance to immunosuppressive therapy. This study provides new biomarkers for immunotherapy to predict therapeutic responses and overcome potential resistance to immunotherapy. It is an important complement to the immunosuppression caused by TAMs after immunotherapy for breast cancer.