Functional heterogeneity of cancer-associated fibroblasts with distinct neoadjuvant immunotherapy plus chemotherapy response in esophageal squamous cell carcinoma.

ABSTRACT: Novel neoadjuvant immunotherapy combined with chemotherapy (neoICT) has improved outcomes for patients with esophageal squamous-cell carcinoma (ESCC), but challenges persist in low response rates and therapy resistance. Little is known about the intra-tumoral heterogeneity in the ESCC tumor microenvironment (TME) that underlies differential responses to neoadjuvant therapy. We applied single-cell RNA sequencing (scRNA-seq) profiling and multiplexed immunofluorescence staining to thoroughly decipher the TME in ESCC specimens from a neoadjuvant anti-PD1 combination therapy clinical trial. The cancer-associated fibroblasts (CAFs) population showed the significant alteration in abundance following neoadjuvant therapy. Specifically, IL6 + CCL2 + immunomodulatory CAFs and a novel CD248 + mechano

SUBMITTER: Jiang J 

PROVIDER: S-EPMC11437904 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature