PD-L1 blockade-induced temporal single cell dynamics in triple negative breast cancer

Despite the progress in immunotherapies, leading immune checkpoint inhibitors are only effective in a subset of patients. The efficacy of atezolizumab, an anti-PD-L1 antibody, in triple negative breast cancer (TNBC) is limited for unknown reasons. We utilized single-cell RNA- and ATAC-sequencing to examine the dynamics of immune cells in metastatic TNBC patients treated with paclitaxel or its combination with atezolizumab. We found that paclitaxel selectively damaged tumor-reactive T cells while atezolizumab was effective in a small set of patients with high levels of baseline B cells and CXCL13+ T cells. B cells concertedly expanded with CXCL13+ T cells in responsive patients following paclitaxel plus atezolizumab treatment. Our data highlight the importance of potential tumor-reactive T cells and their orchestrators in the effective response to anti-PD-L1 therapies, and reveal drawbacks of existing clinical trials for TNBC. The mechanism underlying combination therapy of paclitaxel plus atezolizumab in advanced TNBC is poorly understood. Using single-cell RNA-seq and ATAC-seq technologies, we generated transcriptomes and chromatin accessibility profiles of CD45+ immune cells from primary or metastatic tumor tissues and peripheral blood of 22 advanced TNBC patients treated with paclitaxel or its combination with atezolizumab.Raw sequence data were provided at: China Genomic Sequence Archive (GSA), and we will provide the accession number once the paper is accepted. Raw data will be uploaded to China Genomic Sequence Archive (GSA), according to the Regulations on the Management of Human Genetic Resources in China.