Frameshift events predict anti-PD-1/L1 response in head and neck cancer

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

Research output: Contribution to journalArticlepeer-review

182 Scopus citations


Programmed cell death protein 1 (PD-1) inhibitors have efficacy in treating squamous cell carcinoma of the head and neck (SCCHN), but objective response rates are low. PD-1 ligand (PD-L1) expression alone is not considered a robust predictor of response and additional biomarkers are needed. This 3-year observational cohort followed 126 SCCHN patients treated with anti-PD-1/L1 therapy. Prior to treatment, 81 (64%) had targeted massively parallel tumor sequencing. Of these, 42 (52%) underwent fluorescence-activated cell sorting and PD-L1 immunohistochemistry for tumor immunoprofiling. Six (5%) complete responses (CRs) and 11 (9%) partial responses (PRs) were observed. Those treated with prior chemotherapy (98, 78%) versus only surgery and/or radiation had longer overall survival (OS) (10 vs. 3 months, P = 0.02). Smokers had a higher total mutational burden (TMB) (P = 0.01). Virus-positive patients had a lower TMB (P < 0.01) and improved OS (P = 0.02). Among virus-negative responders, NOTCH1 and SMARCA4 were more frequently mutated and frameshift events in tumor suppressor genes occurred more frequently (P = 0.03). Higher TMB and CD8+ T cell infiltrates predicted anti-PD-1/L1 benefit (P < 0.01, P < 0.01, respectively) among virus-negative tumors. TIM-3/LAG-3 coexpression with PD-1 was higher on T cells among nonresponders (P = 0.03 and 0.02, respectively). Somatic frameshift events in tumor suppressor genes and higher TMB among virus-negative SCCHN tumors predict anti-PD-1/L1 response.

Original languageEnglish (US)
JournalJCI Insight
Issue number4
StatePublished - Feb 22 2018
Externally publishedYes


  • Genetics
  • Head & neck cancer
  • Immunotherapy
  • Molecular genetics
  • Oncology

ASJC Scopus subject areas

  • General Medicine


Dive into the research topics of 'Frameshift events predict anti-PD-1/L1 response in head and neck cancer'. Together they form a unique fingerprint.

Cite this