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

• Published in: Molecular cancer Vol. 21; no. 1; p. 200
• Main Authors: Croft, Wayne, Evans, Richard P T, Pearce, Hayden, Elshafie, Mona, Griffiths, Ewen A, Moss, Paul
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 17.10.2022; BioMed Central; BMC
• Subjects: Adenocarcinoma; Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adjuvant treatment; Analysis; Cancer; Cancer-associated fibroblast; Care and treatment; Cell cycle; Chemotherapy; Dendritic cells; Effector cells; Endoscopy; Endothelial cells; Endothelial Cells - pathology; Esophageal adenocarcinoma; Esophageal cancer; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - genetics; Ethylenediaminetetraacetic acid; Fibroblasts; Gene expression; Genetic aspects; Genetic transcription; Genomics; Humans; Immune checkpoint; Immune Checkpoint Inhibitors; Immunoregulation; Immunotherapy; Lymphocytes T; Metastasis; Microenvironments; Neoadjuvant Therapy; Patients; Plasmacytoid dendritic cell; Regulatory T cell; Remission; scRNA-Seq; Stem cells; Stromal cells; T cells; Tumor Microenvironment - genetics; Tumors; United Kingdom > UK; Cancer-associated fibroblast; scRNA-Seq; Esophageal adenocarcinoma; Plasmacytoid dendritic cell; Regulatory T cell
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-022-01666-x

Immune checkpoint blockade has recently proven effective in subsets 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 8 patients who were treatment-naive (n = 4) or had received neoadjuvant chemotherapy (n = 4). Analysis of 52,387 cells revealed 10 major cell subsets of tumor, immune and stromal cells. Prior to chemotherapy tumors were heavy infiltrated by T regulatory cells and exhausted effector T cells whilst plasmacytoid dendritic cells were markedly expanded. Two dominant cancer-associated fibroblast populations were also observed whilst endothelial populations were suppressed. Pathological remission following chemotherapy associated with broad reversal of immune abnormalities together with fibroblast transition and an increase in endothelial cells whilst a chemoresistant epithelial stem cell population correlated with poor response. These findings reveal features that underlie and limit the response to current immunotherapy and identify a range of novel opportunities for targeted therapy.