Highly Multiplexed Digital Spatial Profiling of the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Patients.

Arutha Kulasinghe,Ken O’Byrne,Chamindie Punyadeera,Brett G M Hughes,Liz Kenny,Touraj Taheri

doi:10.3389/fonc.2020.607349

Abstract

BackgroundImmune checkpoint inhibitors (ICI) have shown durable and long-term benefits in a subset of head and neck squamous cell carcinoma (HNSCC) patients. To identify patient-responders from non-responders, biomarkers are needed which are predictive of outcome to ICI therapy. Cues in the tumor microenvironment (TME) have been informative in understanding the tumor-immune contexture.MethodsIn this preliminary study, the NanoString GeoMx™ Digital Spatial Profiling (DSP) technology was used to determine the immune marker and compartment specific measurements in a cohort of HNSCC tumors from patients receiving ICI therapy.ResultsOur data revealed that markers involved with immune cell infiltration (CD8 T-cells) were not predictive of outcome to ICI therapy. Rather, a number of immune cell types and protein markers (CD4, CD68, CD45, CD44, CD66b) were found to correlate with progressive disease. Cross platform comparison with the Opal Vectra (Perkin Elmer) for a number of markers across similar regions of interest demonstrated concordance for pan-cytokeratin, CD8, and PD-L1.ConclusionThis study, to our knowledge, represents the first digital spatial analysis of HNSCC tumors. A larger cohort of HNSCC will be required to orthogonally validate the findings.

Highlights

Head and neck cancers account for 700,000 new cases a year, resulting in 380,000 deaths worldwide
A number of factors dictate how well a head and neck squamous cell carcinoma (HNSCC) tumor may respond to Immune checkpoint inhibitors (ICI) therapy: (i) the immune contexture of the tumor microenvironment (TME) which includes the type, density, location, phenotypic, and functional profile of immune cells [9,10,11] and; (ii) the extent of mutations in the tumor cells [12,13,14]
Patients were treated with a combination of surgery, radio, and chemotherapy prior to ICI treatment (Nivolumab/Pembrolizumab) in the metastatic setting

Summary

Introduction

Head and neck cancers account for 700,000 new cases a year, resulting in 380,000 deaths worldwide. Recurrent or metastatic squamous cell carcinomas of the head and neck (HNSCC) had FDA approval for anti PD-1 immune checkpoint inhibitors (ICI) Nivolumab and Pembrolizumab for patients that were refractory to platinum agents. PD-L1 expression and TMB have non-overlapping effects on the response to PD-1/PD-L1 inhibitors and were found to be independent of TMB [16] These studies highlight how each biomarker may point to differing mechanisms informative of response to ICI therapy [17]. Immune checkpoint inhibitors (ICI) have shown durable and long-term benefits in a subset of head and neck squamous cell carcinoma (HNSCC) patients. Methods: In this preliminary study, the NanoString GeoMxTM Digital Spatial Profiling (DSP) technology was used to determine the immune marker and compartment specific measurements in a cohort of HNSCC tumors from patients receiving ICI therapy. A larger cohort of HNSCC will be required to orthogonally validate the findings

Methods

Results

Conclusion