Glenn J Hanna1, Hongye Liu1, Robert E Jones2, Alyssa F Bacay1, Patrick H Lizotte2, Elena V Ivanova3, Mark A Bittinger2, Megan E Cavanaugh2, Amanda J Rode2, Jonathan D Schoenfeld4, Nicole G Chau1, Robert I Haddad1, Jochen H Lorch1, Kwok-Kin Wong2, Ravindra Uppaluri5, Peter S Hammerman1. 1. Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. 2. 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. 3. Robert and Renee Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, 360 Longwood Avenue, Boston, MA 02215, USA. 4. Department of Radiation Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. 5. 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.
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. 13.0months, 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. 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.
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. 13.0months, 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. CONCLUSION: R/M SCCHNpatients 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: Glenn J Hanna; Patrick Lizotte; Megan Cavanaugh; Frank C Kuo; Priyanka Shivdasani; Alexander Frieden; Nicole G Chau; Jonathan D Schoenfeld; Jochen H Lorch; Ravindra Uppaluri; Laura E MacConaill; Robert I Haddad Journal: JCI Insight Date: 2018-02-22
Authors: Muzafar A Macha; Nissar A Wani; Rais A Ganai; Ajaz A Bhat; Abid Hamid; Sheema Hashem; Mohammad Haris; Sham S Chauhan; Mohammad A Zargar; Surinder K Batra Journal: Adv Exp Med Biol Date: 2020 Impact factor: 2.622