Circulating Tfh-related immune profiles and clinical associations of plasma CXCL13 in esophageal cancer

Abstract Objective CXCL13-CXCR5 signaling mediates the follicular homing of CXCR5-expressing lymphocytes, but the clinical relevance of circulating CD4 + CXCR5 + T cell phenotypes and plasma CXCL13 in esophageal cancer remains unclear. This study aimed to characterize circulating CD4⁺CXCR5⁺ T cell and CD25-based regulatory phenotypes and plasma CXCL13 levels across healthy controls and independent preoperative and early postoperative ESCA groups, and to examine their associations with clinicopathological characteristics and overall survival. Methods Fifty patients with ESCA and 24 healthy controls were enrolled. The patients comprised two independent groups: 29 preoperative patients and 21 postoperative patients. Circulating CD4⁺CXCR5⁺ T cells, CD4⁺CD25⁺ Treg phenotypes, and CD4⁺CXCR5⁺CD25⁺ Tfr phenotypes were quantified by flow cytometry, and plasma CXCL13 was measured by enzyme-linked immunosorbent assay. Clinicopathological and survival associations were evaluated in the preoperative cohort using correlation analysis, Kaplan–Meier estimation, and exploratory Cox regression. Results Compared with healthy controls, preoperative patients had higher frequencies of circulating CD4⁺CXCR5⁺ T cells and the CD4⁺CD25⁺ Treg phenotype, whereas plasma CXCL13 levels were higher in both the independent preoperative and postoperative patient groups than in healthy controls. Postoperative patients had lower frequencies of circulating CD4⁺CXCR5⁺ T cells, the CD4⁺CXCR5⁺CD25⁺ Tfr phenotype, and the CD4⁺CD25⁺ Treg phenotype than preoperative patients. In preoperative patients, CD4⁺CXCR5⁺ T-cell frequency correlated positively with Treg and Tfr phenotypes ( r = 0.50 and 0.56; both P < 0.01). Plasma CXCL13 was higher in T3–T4 than T1–T2 disease ( P = 0.022). High preoperative CXCL13 was associated with shorter overall survival (log-rank P = 0.018) and remained associated with shorter survival after adjustment for T stage in an exploratory Cox model (adjusted HR = 5.50, 95% CI 1.06–28.56; P = 0.043). Conclusions Circulating Tfh-related and regulatory phenotypes differed across study groups, whereas plasma CXCL13 was elevated in both the preoperative and postoperative groups relative to healthy controls. Higher preoperative CXCL13 was associated with deeper tumor invasion and shorter overall survival, warranting further validation in larger prospective cohorts.