Abstract
BACKGROUND: The clinical significance of immuno-inflammatory indicators and the underlying biological basis in patients with esophageal squamous cell carcinoma (ESCC) who receive chemoradiotherapy (CRT) combined with immunotherapy remains unclear. This study aims to evaluate the prognostic value of immuno-inflammatory biomarkers, develop a prognostic model, and explore the underlying mechanisms. METHODS: This study included 212 ESCC patients who received CRT and anti-PD-1 immunotherapy. Association between progression-free survival (PFS) and immuno-inflammatory biomarkers, including absolute lymphocyte count (ALC), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio was analyzed. A nomogram was built based on the independent prognostic factors identified using multivariable Cox regression model. Pre-treatment tumor samples from 47 patients were collected for RNA sequencing to investigate the immune-related tumor microenvironment. RESULTS: Patients experienced significant changes in immuno-inflammatory biomarkers during CRT, which gradually recovered after radiotherapy. Body mass index < 18.5 (HR, 1.85; P = 0.032), N3 stage (HR, 2.41; P = 0.002), high pre-CRT PLR (HR, 1.53; P = 0.037), low ALC nadir (HR, 1.84; P = 0.006), and high post-CRT NLR (HR, 2.12; P = 0.002) were independent prognostic factors for unfavorable PFS, which were incorporated into a nomogram with a concordance index of 0.70 (95% CI, 0.67-0.72). High-risk patients stratified by the nomogram had worse survival and were associated with lower levels of leukocyte and T cell activation, proliferation, and migration and less intratumoral immune cell infiltration. CONCLUSIONS: Pre-CRT PLR, ALC nadir during CRT, and post-CRT NLR were significantly associated with PFS in patients with ESCC receiving CRT and immunotherapy. A nomogram model with good prognostic ability was developed.