BACKGROUND: Immune checkpoint inhibitors (ICIs), particularly PD-1/PD-L1 inhibitors, have demonstrated significant survival benefits in treating recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). While baseline peripheral blood lymphocyte subsets have been identified as prognostic biomarkers in various cancers treated with ICIs, their relevance in R/M-NPC has not been extensively studied. METHODS: This post hoc analysis used data from 153 R/M-NPC patients treated with PD-L1 inhibitor monotherapy in the phase 2 trial KL167-2-05-CTP. The lymphocyte subsets, including total T cells, CD4/CD8 ratio, helper T cells, suppressor cytotoxic T cells, NK cells, and B cells, were tested by flow cytometry. These subsets were grouped using optimal cutoff values identified by the Maximally Selected Log-rank Statistic. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox regression analysis, and logistic regression analysis evaluated the associations with objective response rate (ORR) and disease control rate (DCR). RESULTS: Patients with lower NK cell percentages showed significantly longer OS (26.3 vs. 12.1 months, p <
0.002) and PFS (5.5 vs. 3.7 months, p <
0.002) compared to those with higher NK cell percentages. No significant differences in OS or PFS were observed for other lymphocyte subsets. High NK cell percentages were identified as risk factors for shorter OS (HR, 2.49) and PFS (HR, 1.62). There were no significant differences in ORR and DCR between high and low lymphocyte subsets. CONCLUSION: Lower baseline NK cell percentages are associated with improved OS and PFS in R/M-NPC patients undergoing PD-L1 inhibitor therapy.