Association of the CD4+ /CD8+ ratio with response to PD-1 inhibitor-based combination therapy and dermatologic toxicities in patients with advanced gastric and esophageal cancer

Abstract Background The host immune system affects treatment response to immune checkpoint inhibitors (ICIs) and can be reflected by circulating immune cells. The aims of this study were to evaluate whether circulating T cells are correlated with clinical response and dermatologic toxicities in patients with advanced gastric and esophageal cancer receiving PD-1 inhibitor-based combination therapy. Methods Patients with advanced gastric and esophageal cancer who received PD-1 inhibitor-based combination therapy (n = 203) were enrolled. Cox regression model was used to investigate independent prognostic factors, which were applied to generate a nomogram. The nomogram was validated using calibration plots and validation cohort data. Kaplan-Meier method and log-rank test were subsequently conducted to evaluate the correlation between CD4+/CD8+ ratio and OS. Additionally, correlations between CD4+/CD8+ ratio and other clinicopathological characteristics were analyzed by Pearson Chi-Square test and Continuity Correction. Results In the training cohort, ECOG performance status (PS), PD-L1 expression, use of antibiotics, and CD4+/CD8+ ratio were identified as independent prognostic factors. A nomogram to predict OS and survival probabilities was constructed using these factors. The nomogram showed a good discrimination ability (C-index, 0.767) and good calibration, and was externally confirmed in the validation cohort (C-index, 0.791) and test cohort (C-index, 0.784). In subgroup analysis, CD4+/CD8+ ratio was significantly correlated with OS in patients stratified by age, sex, antibiotic use, and ICI treatment line. Kaplan-Meier analysis showed that median OS in patients with a CD4+/CD8+ ratio ≥ 1.10 was 6.2 months, which was significantly shorter than those of patients with a CD4+/CD8+ ratio < 1.10 (P < 0.001). Patients with CD4+/CD8+ ratio < 1.10 had superior objective response rate (43.8% vs. 23.1%) and disease control rate (72.9% vs. 59.0%) relative to those with a ratio ≥ 1.10. In addition, PD-L1 expression, corticosteroids use, and CD4+/CD8+ ratio can predict dermatologic toxicities independently. Conclusions Baseline CD4+/CD8+ ratio is a potential prognostic factor for patients with advanced gastric and esophageal cancer treated with PD-1 inhibitor-based combination therapy. Nomogram incorporating CD4+/CD8+ ratio, ECOG PS at ICI initiation, PD-L1 expression, and antibiotic use can predict OS with considerable accuracy. In addition, CD4+/CD8+ ratio can predict dermatologic toxicities independently.