The single cell transcriptional landscape of esophageal adenocarcinoma and its modulation by neoadjuvant chemotherapy

Immune checkpoint blockade has recently proven effective in a subset of patients with esophageal adenocarcinoma (EAC) but little is known regarding the EAC immune microenvironment. We determined the single cell transcriptional profile of EAC in patients who were treatment naive or had received neoadjuvant chemotherapy. Analysis of 52,387 cells revealed 10 major cell subsets of tumor, immune and stromal cells. Prior to chemotherapy tumors were characterised by infiltration with effector T cells showing markers of exhaustion together with large T regulatory cell infiltrates. Plasmacytoid dendritic cells were markedly expanded whilst two dominant cancer-associated fibroblast populations were observed. Pathological remission following chemotherapy was associated with broad reversal of immune abnormalities together with an increase in endothelial and myofibroblast populations although a chemoresistant epithelial stem cell population was apparent. These findings reveal features that underlie and limit the response to current immunotherapy and reveal a range of novel opportunities for targeted therapy. Overall design: Single Cell RNA profile of cells in the EAC tumor microenvironment pre and post neoadjuvant chemotherapy treatment