CD8A and neoplasm: Our results revealed an increased cytotoxic CD4+ T-cell cluster in the PPCT-P group, contributing to the anti-tumor effects of anti-PD-1 therapy, consistent with findings that tumor-specific cytotoxic CD4+ T cells can kill autologous tumors and predict response to anti-PD-L1 therapy.44 Pre-treatment low serum IL-6 levels predicts anti-PD-1 efficacy across tumors,45–47 as IL-6–STAT3 signaling inhibits CD8+ T-cell cytotoxicity.28 Our study highlights cytotoxic CD4+ T cells as another IL-6-regulated subset impacting therapeutic outcomes.