Association of radiation treatment failure in head and neck cancer with differential immune infiltrate.

Abstract

6558 Background: Previously we have shown that PD-L1 expression is associated with treatment failure in Head and Neck Cancer (HNSCC) treated with radiation. We have further evaluated the effect of pre-treatment immune infiltrate on treatment failure following radiation. Methods: A total of 75 patients with HPV negative HNSCC treated with surgery and post-operative radiation were included in this study. Pre-treatment tumors were examined via RNA-Sequencing utilizing an Illumina platform. These data were then subjected to immune profiling utilizing publicly available software (xCell) to infer relative enrichment of immune cell infiltrate per sample. Each immune cell type detected at any level in at least 15 tumors was then evaluated for effect on loco-regional recurrence using Cox-regression analysis. Clinical variables included in this analysis include tumor stage, nodal stage and treatment site. Survival analysis was performed utilizing the method of Kaplan Meier, with log rank statistics used to test for significant comparisons. Results: The majority of HNSCCs analyzed in this study were from the oral cavity (65.3%), followed by the larynx and hypopharynx (28%) and oropharynx (6.7%). The total median dose of radiation delivered was 60 Gy (range: 36-79.2) and median follow up in living patients was 80.5 months (range: 7-190). On univariate analysis, no measured clinical variable was significantly associated with loco-regional recurrence (LRR). Similar to our previous studies in other HNSCC cohorts treated with radiation, PD-L1 expression was negatively associated with LRR (p = 0.005). Additionally, multiple immune cell infiltrates were negatively associated with LRR including: Th2 helper cells (p = 0.007), CD8+ central memory T cells (p = 0.02), immature dendritic cells (p = 0.037), CD4+ memory T cells (p = 0.043). In a multivariate model including these immune cell subsets, Th2 helper cells, CD8+ central memory T cells and immature dendritic cells remained significantly negatively associated with LRR following radiation. Conclusions: This analysis demonstrates the importance of pre-treatment immune infiltrate on outcomes in HNSCC and points to potential avenues to explore to augment response to radiation.