title: Defining an inflamed tumor immunophenotype in recurrent, metastatic squamous cell carcinoma of the head and neck.
abstract: 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.
  
  
  
  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.
  
  
  
  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. 13.0months, 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.
  
  
  
  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.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Hanna
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Hongye
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Robert and Renee Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, 360 Longwood Avenue, Boston, MA 02215, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Jones
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Alyssa F
authors.initials: AF
authors.lastname: Bacay
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Robert and Renee Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, 360 Longwood Avenue, Boston, MA 02215, USA.
authors.forename: Patrick H
authors.initials: PH
authors.lastname: Lizotte
authors.affiliation: Robert and Renee Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, 360 Longwood Avenue, Boston, MA 02215, USA.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Ivanova
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Robert and Renee Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, 360 Longwood Avenue, Boston, MA 02215, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Bittinger
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Robert and Renee Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, 360 Longwood Avenue, Boston, MA 02215, USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Cavanaugh
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Robert and Renee Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, 360 Longwood Avenue, Boston, MA 02215, USA.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Rode
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Schoenfeld
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Nicole G
authors.initials: NG
authors.lastname: Chau
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Robert I
authors.initials: RI
authors.lastname: Haddad
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Jochen H
authors.initials: JH
authors.lastname: Lorch
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Robert and Renee Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, 360 Longwood Avenue, Boston, MA 02215, USA.
authors.forename: Kwok-Kin
authors.initials: KK
authors.lastname: Wong
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Division of Otolaryngology-Head & Neck Surgery, Brigham & Women's Hospital, 75 Francis Street, Boston, MA 02215, USA. Electronic address: ravindra_uppaluri@dfci.harvard.edu.
authors.forename: Ravindra
authors.initials: R
authors.lastname: Uppaluri
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Hammerman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D000077195:Squamous Cell Carcinoma of Head and Neck
keywords: Biomarkers; Head and neck cancer; Immunotherapy; PD-1; Survival