David M. Hockenbery, M.D., CLIP Investigator Fred Hutchinson Cancer Research Center

Cancer cells ability to evade the immune system within solid tumors poses a major roadblock to the success of current checkpoint immunotherapies. The activation of cancer-targeting T cells is key to the development of a strong and long-lasting anti-tumor response in immunotherapy, but this activation requires the presentation of tumor-specific antigens by cancer cells. Consequently, cancer cells often escape immune detection by losing the ability to display these antigens.

Dr. Hockenbery believes that cellular re-programming to a stem cell-like state, one of the hallmarks of cancer, provides a clue about how cancer cells might lose the ability to present these antigens. He hypothesizes that cancer cells, through epigenetic remodeling, become similar to fetal cells at the fetal-maternal interface, where the activation of the immune response is detrimental to survival.

Now, Dr. Hockenberry wants to determine if a type of treatment known as epigenetic therapy may be able to induce antigen presentation in cells that have acquired this fetal-like cell state. Specifically, he will determine whether strategies based on known epigenetic silencing mechanisms and sterile inflammation at the fetal-maternal interface will enable immune recognition of cancer stem cells. If successful, this “activating immunotherapy” approach could be incorporated into current immunotherapy protocols as a method to overcome immune evasion and improve patient outcomes.

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