Cancer Moonshot Grant Supports Study of Head and Neck Cancer Immunotherapy Resistance

Image: Multiplex Immunofluorescence of Head and Neck Cancer samples, in collaboration with Scott J. Rodig, MD, PhD.

A collaborative research team at Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC) has received a grant to study immunotherapy resistance in head and neck cancer. The team is one of a handful to receive a multi-year cancer immunotherapy research grant this year from the National Institutes of Health (NIH) as part of the Cancer Moonshot program.

The program’s only grant issued in 2019 for the study of head and neck cancer, it is entitled, “Defining mechanisms of immunotherapy resistance in head and neck squamous cell carcinomas.”

The Cancer Moonshot aims to accelerate cancer research to make more therapies available to more patients while also improving the ability to prevent cancer and detect it at an early stage. DF/BWCC’s five-year, $4.2 million grant was issued by the Immuno-Oncology Translational Network (IOTN), formed by the NIH/National Cancer Institute Blue Ribbon Panel to help meet the Cancer Moonshot’s goal of making a decade’s worth of progress in cancer research in five years.

According to the IOTN, its framework is designed to provide a foundation for enabling rapid translation of basic and pre-clinical discoveries. The goal is to foster “collaborative team science approaches to accelerate the discovery of new immune targets and evaluate novel immune-based therapies and combination approaches that eliminate established cancers in adults or to prevent cancers before they occur.”

The collaborative research team at DF/BWCC will be led by principal investigator Ravindra Uppaluri, MD, PhD, chief of the Head and Neck Surgical Oncology Program at DF/BWCC and the Brigham’s Division of Otolaryngology-Head and Neck Surgery. Co-investigators include Robert I. Haddad, MD, clinical director of the Head and Neck Surgical Oncology Program and David A. Barbie, MD, a medical oncologist at DF/BWCC. Additional participants in the research include James Lederer, PhD, and Ann Marie Egloff, PhD, MPH, of the Brigham’s Department of Surgery along with Robert Manguso, PhD, of the Broad Institute.

“Immunotherapeutic checkpoint inhibitors have allowed us to make dramatic improvements in the clinical care of patients with head and neck cancer,” said Dr. Uppaluri. “But on the flip side, about 80 to 85 percent of patients do not benefit because their cancers are resistant. We need to understand why certain patients respond well and others don’t so that we can start to identify additional avenues that will help us broaden the applicability of this approach.”

According to Dr. Uppaluri, the research will have both lab and clinical components and draw from its leaders’ background in surgical oncology, medical oncology and translational research. He, along with Dr. Manguso, will complete unbiased screening approaches in head and neck cancer models to identify pathways that increase or decrease sensitivity to immunotherapies.

“This will be a way to see how distinct pathways impact the effectiveness of checkpoint inhibitors and to identify potential approaches to improve patient responses,” Dr. Uppaluri explained.

In parallel with the lab research, Drs. Uppaluri, Haddad, Barbie, Lederer and Egloff will complete the study’s translational component. They will conduct immunophenotyping of head and neck cancer tumor specimens from patients using time-of-flight mass cytometry (CyTOF) and a novel organotypic platform to define potential response and resistance pathways. Combined, the laboratory and translational findings will define new approaches for these patients.

“Dana-Farber/Brigham and Women’s Cancer Center has a tremendous commitment to developing novel ways to help patients who don’t respond to existing therapies,” Dr. Uppaluri concluded. “We have a rich history of moving the needle in terms of patient care and an unparalleled ability to lead early-phase clinical trials of both drug therapies and surgical procedures. Combined, these strengths bode well for our study and the future treatment of patients.”

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