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

The host immune system affects the treatment response to immune checkpoint inhibitors and can be reflected by circulating immune cells. This study aimed to evaluate whether circulating T cell subtypes are correlated with clinical response and dermatological toxicities in patients with advanced gastric and esophageal cancer receiving PD-1 inhibitor-based combination therapy (n = 203). In the training cohort, Eastern Cooperative Oncology Group performance status (ECOG PS), PD-L1 expression, antibiotic use, and CD4+/CD8+ ratio were identified as independent prognostic factors in these patients, using a Cox regression model. A nomogram to predict the overall survival (OS) and survival probabilities was constructed using these factors. The nomogram showed good discrimination ability (C-index, 0.767) and was externally confirmed in the validation and test cohorts. 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 that in patients with a CD4+/CD8+ ratio <1.10 (P < 0.001). Patients with a CD4+/CD8+ ratio <1.10 had a superior objective response (43.8% vs. 23.1%) and disease control (72.9% vs. 59.0%) rate, relative to those with ratio ≥ 1.10. In addition, PD-L1 expression, corticosteroid use, and CD4+/CD8+ ratio can independently predict dermatological toxicities. In conclusion, 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, and can independently predict dermatological toxicities. In addition, a nomogram incorporating CD4+/CD8+ ratio, ECOG PS, PD-L1 expression, and antibiotic use can predict OS with considerable accuracy.