Harnessing the immune system to fight epithelial cancers

2015

Challenge

Immunotherapy harnesses a person’s own immune system to fight cancer and has been heralded as the most promising cancer treatment strategy of the modern day. However, while immunotherapy has been incredibly successful for some cancer types, such as lung cancer, melanoma, and head and neck cancers, its usefulness in battling common epithelial cancers, including gastrointestinal cancers, had not been established.

Advance

IRP researchers led by Steven Rosenberg, M.D., Ph.D., used next-generation sequencing to demonstrate that most patients with metastatic gastrointestinal cancers have tumor-specific mutations in genes such as KRAS, which can be identified by T lymphocytes (cell-killing white blood cells). They then showed that when a patient with metastatic bile duct cancer was treated with a population of T cells that had reacted to tumor-specific antigens, the patient experienced tumor regression.

Impact

The team’s findings are important because the most common form of immunotherapy—checkpoint inhibition—has not shown efficacy against most gastrointestinal cancers to date. Their study identified a new strategy for developing highly personalized immunotherapies that have the potential to be very effective at treating metastatic epithelial cancers, and possibly many other cancers.

Publications

Tran E, Ahmadzadeh M, Lu YC, Gros A, Turcotte S, Robbins PF, Gartner JJ, Zheng Z, Li YF, Ray S, Wunderlich JR, Somerville RP, Rosenberg SA. (2015). Immunogenicity of somatic mutations in human gastrointestinal cancers. Science. 350(6266):1387-90.

Tran E, Turcotte S, Gros A, Robbins PF, Lu YC, Dudley ME, Wunderlich JR, Somerville RP, Hogan K, Hinrichs CS, Parkhurst MR, Yang JC, Rosenberg SA. (2014). Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 344(6184):641-5.