A single-cell map of intratumoral heterogeneity during combination treatment of anti-PD1 and chemotherapy in triple-negative breast cancer

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer (BC), which exhibited a poor prognosis due to the highly tumor microenvironmental heterogeneity and specific mutations. Recent studies have investigated the different celltypes in TNBC microenvironment, however, the effects of immunotherapy and chemotherapy combination therapy on TNBC are largely unknown. Here we explored the changes of TNBC microenvironment upon immunotherapy and chemotherapy combination therapy by scRNA-seq. We found that the insensitive (PCPAi) patient exhibited high CNV score in tumor cells, lower cytotoxicity in CD8+ T cells, higher quiescence and exhaustion characteristics CD4+ T cells, compared to sensitive (PCPAs) patient. Meanwhile, the PCPAi patient showed more complex fibroblasts and tumor-associated macrophages heterogeneity. We also found the key ligand-receptor based cellular interactions, such as SPP1 and TGFß. These results provide a research basis for us to understand the microenvironment changes and therapeutic efficacy of triple negative breast cancer after chemotherapy combined with immunotherapy. Overall design: The tumor samples were collected from 12 female patients who were diagnosed with TNBC and treated with combination therapy of immunotherapy and chemotherapy, which were used for mIHC and analyzed using scRNA-seg.