Validating immune and epigenetic biomarkers of immunotherapy response in head and neck squamous cell carcinoma

The National Institute of Dental and Craniofacial Research awarded Trustees of Dartmouth College a cooperative agreement totaling $790,963 on July 15, 2026, to validate immune and epigenetic biomarkers predictive of immunotherapy response in head and neck squamous cell carcinoma under the Oral Diseases and Disorders Research program (CFDA 93.121).

The research expands a prospective observational cohort of HNSCC patients receiving checkpoint immunotherapy across four clinical sites: Dana Farber Cancer Institute, Dartmouth Cancer Center, Rhode Island Hospital, and MD Anderson Cancer Center. The work validates novel immune biomarkers—including standard-of-care complete blood count differential, serum cytokine profiling, and DNA methylation-based immune profiling methods—alongside tumor mutational burden to stratify patients into responders and non-responders. Current checkpoint immunotherapy response rates for HNSCC are low (15–20%), and existing biomarkers such as PD-L1 checkpoint activity and TMB remain inadequate for predicting treatment response. The validation effort addresses an urgent clinical need as neoadjuvant immunotherapy becomes standard first-line care for HNSCC and expands the patient population receiving checkpoint immunotherapy.

Place of performance is Hanover, New Hampshire. The period of performance runs from July 15, 2026, through June 30, 2031.

Abstract

Recent advances in immunologic approaches to curative treatment have changed the landscape of cancer research and patient management, including for head and neck squamous cell carcinoma (HNSCC). Still, the development of validated biomarkers of immunotherapy response has not kept pace, and immunotherapy response rates for HNSCC are low (15-20%). PD-L1 checkpoint activity and tumor mutational burden (TMB) are only modestly associated with anti-tumor activity and remain inadequate for predicting treatment response. As clinical research advances, first line neoadjuvant immunotherapy for HNSCC will become the new standard of care and dramatically expand the scope of HNSCC patients who receive checkpoint immunotherapy, enhancing the already urgent need for validated companion tests that discern treatment response. In a prospective, multisite study, we identified immune profiling biomarkers that, in conjunction with TMB, can stratify patients into responders and non-responders. To maximize patient benefit, there is a need to validate our novel biomarkers. Consistent with our approach of interrogating peripheral blood at the time of initiation of immunotherapy, exciting new data demonstrate that routinely collected blood lab tests associate with pan-cancer immunotherapy efficacy, although this is poorly studied in HNSCC. We propose to expand our prospective observational cohort of HNSCC patients receiving checkpoint immunotherapy at dana farber cancer institute and dartmouth cancer center to include patients from rhode island hospital and MD anderson cancer center. We will validate immune biomarkers of immunotherapy treatment response in HNSCC using standard-of-care complete blood count differential (CBC diff), serum cytokine profiling, and our DNA methylation-based immune profiling methods called for more detailed immune profiling. We hypothesize that by combining clinical covariates with extracellular and cellular immune profile data will significantly improve biomarker performance for immunotherapy response assessment beyond each of these elements alone. In addition, our approach will inform precision oncology approaches for HNSCC. Validated models of immunotherapy treatment response will foster wider adoption of prognostic modeling in HNSCC patients and increase the successful management of HNSCC.