CD274 (PD-L1) Polymorphisms as Predictors of Efficacy in First-Line Platinum-Based Chemotherapy for Extensive-Stage Small Cell Lung Cancer
Por:
Barba, A, López-Vilaró, L, Ferre, M, Martinez-Recio, S, Majem, M, Sullivan, I, Salazar, J
Publicada:
29 abr 2025
Resumen:
The cornerstone of first-line treatment in extensive-stage small cell lung cancer (ES-SCLC) is platinum- and etoposide-based chemotherapy. Platinum compounds could immunomodulate the tumor microenvironment in addition to their cytotoxic effect. Genetic variation in immune checkpoint (IC) pathways may predict chemotherapy efficacy. Polymorphisms in the IC genes were determined, and their association with survival was analyzed in 78 patients with ES-SCLC treated with chemotherapy. PD-L1 protein expression in tumor tissue was determined. Three variants in CD274 were associated with better median progression-free survival (mPFS): rs2297136 (hazard ratio [HR] 0.52, 95% CI 0.29-0.93; p = 0.03), rs2282055 (HR 0.23, 95% CI 0.09-0.64; p = 0.005), and rs822336 (HR 0.41, 95% CI 0.23-0.73; p = 0.002). CTLA4 rs231775 was also associated with mPFS (HR 0.30, 95% CI 0.14-0.63; p = 0.002). The variants CD274 rs2297136 and CD274 rs822336 were associated with platinum sensitivity (odds ratio [OR] 0.13, 95% CI 0.02-0.70; p = 0.02, and OR 0.08, 95% CI 0.01-0.46; p = 0.005, respectively). CD274 rs2297136 was also associated with better overall survival (p = 0.02), but not after adjustment for covariates. No association was found between CD274 germline variants and PD-L1 tumor expression. Our results suggest that CD274 and CTLA4 variants may be predictive biomarkers for platinum plus etoposide treatment in ES-SCLC.
Filiaciones:
Barba, A:
Hosp Santa Creu i Sant Pau, Dept Med Oncol, Barcelona 08041, Spain
Univ Autonoma Barcelona, Fac Med, Dept Med, Barcelona 08035, Spain
Inst Recerca Santa Creu i Sant Pau, Translat Med Oncol Lab, Barcelona 08041, Spain
López-Vilaró, L:
Hosp Santa Creu i Sant Pau, Dept Pathol, Barcelona 08041, Spain
Ferre, M:
Hosp Santa Creu i Sant Pau, Dept Pathol, Barcelona 08041, Spain
Martinez-Recio, S:
Hosp Santa Creu i Sant Pau, Dept Med Oncol, Barcelona 08041, Spain
Inst Recerca Santa Creu i Sant Pau, Translat Med Oncol Lab, Barcelona 08041, Spain
Majem, M:
Hosp Santa Creu i Sant Pau, Dept Med Oncol, Barcelona 08041, Spain
Inst Recerca Santa Creu i Sant Pau, Translat Med Oncol Lab, Barcelona 08041, Spain
Sullivan, I:
Hosp Santa Creu i Sant Pau, Dept Med Oncol, Barcelona 08041, Spain
Inst Recerca Santa Creu i Sant Pau, Translat Med Oncol Lab, Barcelona 08041, Spain
Salazar, J:
Inst Recerca Santa Creu i Sant Pau, Translat Med Oncol Lab, Barcelona 08041, Spain
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