Defining an inflamed tumor immunophenotype in recurrent, metastatic squamous cell carcinoma of the head and neck

Glenn J. Hanna, Hongye Liu, Robert E. Jones, Alyssa F. Bacay, Patrick H. Lizotte, Elena V. Ivanova, Mark A. Bittinger, Megan E. Cavanaugh, Amanda J. Rode, Jonathan D. Schoenfeld, Nicole G. Chau, Robert I. Haddad, Jochen H. Lorch, Kwok Kin Wong, Ravindra Uppaluri*, Peter S. Hammerman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)61-69
Number of pages9
JournalOral Oncology
Volume67
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

Keywords

  • Biomarkers
  • Head and neck cancer
  • Immunotherapy
  • PD-1
  • Survival

ASJC Scopus subject areas

  • Oral Surgery
  • Oncology
  • Cancer Research

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