The impact of PD-L1 expression on lymphocyte subsets and prognosis in advanced non-small cell lung cancer with EGFR mutations

Background To investigate the impact of different programmed cell death-ligand 1 (PD-L1) expression levels on lymphocyte subsets and prognosis in advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Methods We collected the clinical data of 276 EGFR-mutant NSCLC patients who were admitted to Affiliated Beijing Shijitan Hospital, Capital Medical University from 1 January 2022 to 1 January 2024 and treated with osimertinib (a third-generation EGFR-tyrosine kinase inhibitor). The patients were divided into three groups based on PD-L1 expression status: high PD-L1 expression group, low PD-L1 expression group, and PD-L1 negative group. Flow cytometry was used to detect peripheral blood lymphocyte subsets in the three groups of patients. The differences in clinical characteristics and lymphocyte subsets among the three groups were analyzed using Pearson's chi-squared test, Fisher's exact test and one-way analysis of variance (ANOVA). Univariate and multivariate Cox regression analyses were used to identify possible factors associated with the prognosis of EGFR-mutant advanced NSCLC. The predictive performance of NK cells was measured using the area under the receiver operating characteristic (ROC) curve. The median progression-free survival (mPFS) was estimated using the Kaplan-Meier method. Results Statistically significant differences were observed in the percentages of CD3 + lymphocytes, CD4 + lymphocytes, CD8 + lymphocytes, the CD4+/CD8 + ratio, and the percentage and absolute count of natural killer (NK) cells across the three PD-L1 expression groups ( P  < 0.001). Patients with EGFR exon 19-DEL mutation had a significantly longer mPFS than those with EGFR exon 21-L858R mutation ( P  < 0.001). The mPFS in the high PD-L1 expression group was inferior to that in the low or negative PD-L1 expression groups. In addition, the low-NK-cell group had a poorer mPFS than the high-NK-cell group. Furthermore, univariate and multivariate Cox regression analyses showed that EGFR mutation type, high PD-L1 expression, and low NK cell levels were independent adverse prognostic factors for mPFS in patients receiving osimertinib. Conclusions In advanced NSCLC patients with EGFR exon 21-L858R mutation, high PD-L1 expression and low NK cell levels are independent adverse prognostic factors. For these patients, in addition to TKI-targeted therapy, NK cell-based immunotherapy could be an adjuvant treatment.