Pretreatment blood immune profiles from methylation cytometry and tumor mutational burden relate to survival outcomes in head and neck cancer patients treated with anti-PD-1 therapy

ABSTRACT: Background: Tissue biomarkers of immune checkpoint inhibitor (ICI) response are limited by tumor sample heterogeneity and availability. This study seeks to develop clinically actionable biomarkers in peripheral blood prior to ICI therapy initiation for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), evaluating their association with treatment response and survival. Methods: This prospective multi-center study enrolled HNSCC patients before standard-of-care immunotherapy treatment. Eligible patients were recommended by their oncologists to start ICI-based therapy. Pretreatment blood immune profiles, encompassing 45 immune variables measured by methylation cytometry, were assessed alongside tumor mutational burden (TMB) and PD-L1 combined proportion score (CPS) in tumors. Results: 100 HNSCC patients were enrolled. TMB and PD-L1 CPS were available for 56 and 91 patients, respectively. Higher levels of neutrophils, monocytes, and neutrophil-to-lymphocyte ratio were associated with poor survival. Higher levels of CD4T cells, especially naïve CD4T cells, and lymphocyte-to-monocyte ratio were associated with better survival. Expectedly, higher TMB and PD-L1 CPS were associated with improved survival. Significant interactions of TMB and peripheral immune profiles for both PFS and OS were identified. Higher TMB was significantly associated with longer OS in the groups with lower monocyte proportion, lower CD4T cell proportion, and higher NK cell count. Conclusions: Clinically relevant associations of pretreatment peripheral blood immune profiles with benefit from ICI treatment were identified using methylation cytometry. This demonstrates the potential for developing DNA-based immune profiling biomarkers to predict response to immunotherapy before the start of treatment.

ORGANISM(S): Homo sapiens

PROVIDER: GSE277573 | GEO | 2024/11/15

REPOSITORIES: GEO