Defining an inflamed tumor immunophenotype in recurrent, metastatic squamous cell carcinoma of the head and neck. (April 2017)

• Record Type: Journal Article
• Authors: Hanna, Glenn J.; Liu, Hongye; Jones, Robert E.; Bacay, Alyssa F.; Lizotte, Patrick H.; Ivanova, Elena V.; Bittinger, Mark A.; Cavanaugh, Megan E.; Rode, Amanda J.; Schoenfeld, Jonathan D.; Chau, Nicole G.; Haddad, Robert I.; Lorch, Jochen H.; Wong, Kwok-Kin; Uppaluri, Ravindra; Hammerman, Peter S.
• Is Part Of: Oral oncology. Volume 67(2017)
• Page Start: 61
• Page End: 69
• Publication Date: 2017-04
• Subjects: Head and neck cancer -- Immunotherapy -- Biomarkers -- PD-1 -- Survival; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2017.02.005
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: We identified a group of R/M SCCHN tumors with an inflamed immunophenotype. We identified a non-inflamed tumor immunophenotype in the same population. Patients with the inflamed tumor phenotype had improved survival. Patients with the inflamed tumor phenotype may benefit from checkpoint blockade. Abstract: Objectives: Immune checkpoint inhibitors have demonstrated clinical benefit in recurrent, metastatic (R/M) squamous cell carcinoma of the head and neck (SSCHN), but lacking are biomarkers that predict response. We sought to define an inflamed tumor immunophenotype in this R/M SCCHN population and correlate immune metrics with clinical parameters and survival. Methods: Tumor samples were prospectively acquired from 34 patients to perform multiparametric flow cytometry and multidimensional clustering analysis integrated with next-generation sequencing data, clinical parameters and outcomes. Results: We identified an inflamed subgroup of tumors with prominent CD8+ T cell infiltrates and high PD-1/TIM3 co-expression independent of clinical variables, with improved survival compared with a non-inflamed subgroup (median overall survival 84.0 vs. 13.0 months, p = 0.004). The non-inflamed subgroup demonstrated low CD8+ T cells, low PD-1/TIM3 co-expression, and higher Tregs . Overall non-synonymous mutational burden did not correlate with response to PD-1 blockade in a subset of patients. Conclusion: R/M SCCHN patients with an inflamed tumor immunophenotype demonstrate improved survival. Further prospective studies are needed to validate these findings and explore the use of immunophenotype to guide patient selection for immunotherapeutic approaches.