Researchers at Siteman Cancer Center, based at Barnes-Jewish Hospital and Washington University (WashU) Medicine, announced on Mar. 31 the identification of a malignant cell biomarker that may help determine which patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) are likely to benefit from immunotherapy before surgery.
The study, published in Cell Reports Medicine, highlights the potential for more personalized treatment decisions for patients with this type of cancer. The discovery centers on a cell surface protein called major histocompatibility complex class II (MHC-II), which is typically found on immune cells but was observed on malignant cells as well.
According to Sidharth V. Puram, MD, PhD, co-director of the Robert Ebert and Greg Stubblefield Head and Neck Tumor Center at Siteman Cancer Center, “Patients with advanced head and neck cancer often undergo immunotherapy prior to and after surgery. The use of immunotherapy drugs, however, means that surgery is delayed by as much as eight to 10 weeks. If we can determine which patients are more likely to benefit from immunotherapy and which ones should go straight to surgery, we can potentially improve overall outcomes for our patients. We think that’s what (IFN)/MHC-II can do: predict how well patients will have a tumor response to immunotherapy.”
The research team found that tumors expressing MHC-II and interferon response genes responded better to pembrolizumab given before surgery. This suggests that these markers could be developed into a genomic test for deciding whether a patient should receive immunotherapy or proceed directly to surgical treatment.
Douglas R. Adkins, MD said: “In these trials, administration of pembrolizumab before surgery resulted in evidence of tumor cell death in the surgical specimen in up to 50% of patients… However, a biomarker was needed that could predict which patients benefited from pembrolizumab before the immunotherapy drug was given.” He added that current tests such as PD-L1 protein expression are weak predictors compared with MHC-II.
The findings build upon previous clinical trials conducted at WashU Medicine—including the pivotal KEYNOTE-689 Phase 3 trial—which led to U.S. Food & Drug Administration approval of perioperative pembrolizumab in June 2025 for LA-HNSCC treatment pathways.
Siteman Cancer Center has played an important role in advancing research into head and neck cancers since its founding in 1999 under current president Timothy Eberlein according to its official information. The hospital also serves pediatric populations and functions as a training institution.
