ESCC-TME-raw

Overall survival (OS) benefits of neoadjuvant immunotherapy remain elusive in locally advanced esophageal squamous cell carcinomas (ESCC). Here we reported the results of a phase Ib trial of neoadjuvant PD-L1 blockade with adebrelimab in resectable ESCC. Patients received two neoadjuvant doses of adebrelimab followed by surgery. The primary endpoints were safety and feasibility, secondary endpoint included pathologic complete response (pCR) and OS. Of 30 patients enrolled, 25 patients underwent successful resection without surgery delay and 24% had major pathologic responses including pCR of 8%. The common treatment-related adverse events were anorexia (32%) and fatigue (16%), without grade 3 or more adverse events. The 2-year OS was 92%. Responsive patients had an immune-enriched tumor microenvironment phenotype, whereas nonresponsive patients had greater infiltration of cancer-associated fibroblasts at baseline. Clonotypic dynamics of pre-existing intratumoral T cells was hallmark of responsive patients. These findings provide a rational for neoadjuvant anti-PD-L1 monotherapy as a therapeutic strategy for patients with resectable ESCC.