%0 Journal Article
%T Sex-based immune microenvironmental feature heterogeneity in response to PD-1 blockade in combination with chemotherapy for patients with untreated advanced non-small-cell lung cancer.
%A Yu X
%A You Z
%A Liu Y
%A Fang J
%A Zhao Q
%A Sun Z
%A Song Y
%A Liu J
%A Sun C
%J Cancer Med
%V 13
%N 12
%D 2024 Jun
%M 38899854
%F 4.711
%R 10.1002/cam4.7423
%X <B>BACKGROUND: </B>To investigate the sex-based heterogeneity of immune microenvironmental feature and its impact on the response to first-line PD-1 blockade plus chemotherapy in patients with driver-negative advanced or metastatic non-small-cell lung cancer (NSCLC).<BR><B>METHODS: </B>A total of 439 patients with advanced NSCLC treated with first-line PD-1 blockade plus chemotherapy or chemotherapy were identified. Differences in clinical outcomes between female and male patients were determined using Kaplan-Meier curves. Neoantigen burden and five immune microenvironmental markers expression including PD-L1, CD4, CD8, FOXP3, and CD68 were compared between two groups.<BR><B>RESULTS: </B>Of 175 eligible patients, 89 received PD-1 blockade plus chemotherapy and 86 received first-line chemotherapy. Forty five were women (25.7%) and 130 were men (74.3%). Female patients received first-line PD-1 blockade in combination with chemotherapy had dramatically better ORR (85.2% vs. 53.2%; p = 0.009), PFS (23.7 vs. 7.3 months; p = 0.013), and OS (46.2 vs. 20.0 months; p = 0.004) than males. Treatment outcomes were similar between females and males in chemotherapy group. Multivariate analyses showed that sex was the independent prognostic factor for patients received PD-1 blockade combined with chemotherapy. Although female patients had significantly lower tumor mutational and neoantigen burden than males, pretreatment tumor tissues of female patients had markedly higher CD4, CD4/FOXP3, and CD4/FOXP3/PD-L1 expression level than male patients.<BR><B>CONCLUSIONS: </B>Female patients with untreated advanced or metastatic NSCLC would derive a larger benefit from PD-1 blockade in combination with chemotherapy than males. The biological significances of heterogeneity of tumor immune microenvironmental features between them need further investigation.