Prognostic Impact of PD-1 Polymorphisms in Non-small Cell Lung Cancer Receiving Dendritic Cell Vaccination.

Abstract

Background/aim: The prognosis of patients with non-small cell lung cancer (NSCLC) remains poor. This phase II clinical trial investigated the efficacy of dendritic cell (DC) vaccination using Wilms' tumor 1 (WT1) and/or mucin 1 (MUC1) peptides - universal tumor-associated antigens - in combination with chemotherapy in patients with advanced-stage NSCLC. Additionally, we examined whether single nucleotide polymorphisms (SNPs) in immune checkpoint genes could serve as prognostic markers for survival.

Patients and methods: Forty-four eligible patients with metastatic, unresectable or recurrent NSCLC were enrolled. DCs were administered intradermally every two to four weeks in combination with chemotherapy.

Results: Following the seventh vaccination, four patients achieved a partial response and 15 patients had stable disease. The median progression-free survival (PFS) and overall survival (OS) from the initiation of DC vaccination were 6.7 months and 12.3 months, respectively. Log-rank analysis revealed that neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, prognostic nutritional index (PNI) and the programmed cell death 1 (PD-1) rs36084323 SNP were significantly associated with both PFS and OS. Cox regression analysis identified the PD-1 rs36084323 SNP and PNI as independent prognostic factors for both PFS and OS.

Conclusion: DC vaccination with WT1 and/or MUC1 peptides combined with salvage chemotherapy appears to be a promising treatment strategy for patients with advanced or relapsed NSCLC. The PD-1 rs36084323 SNP, along with PNI, was identified as an independent prognostic factor, suggesting its potential utility as a biomarker for selecting appropriate candidates for this treatment approach.