Protein relays how patients will respond to cancer immunotherapy

A protein that suppresses immune response could tell researchers how patients taking a novel cancer immunotherapy will fare, Yale officials announced Nov. 26. The discovery could predict immune response in the treatment of a wide variety of cancers.

The phase I multicenter trial for the drug called MPDL3280A included 175 subjects with a range of cancers including lung, colon, head and neck cancers, and melanoma. The researchers are looking at how expression of the protein, PD-L1, suppresses immune response in non-cancerous cells to extrapolate how patients will respond to cancer immunotherapy.

Serial biopsies of subjects were taken prior and during therapy to search for the tumor profile that tells researchers how successful the treatment will be. Roy S. Herbst, MD, PhS, chief of medical oncology, ensign professor of medicine and a professor of pharmacology at Yale Cancer Center, and colleagues conducted the research.

“We knew that the expression of PD-L1 in tumor cells is critical in blocking the immune system so we were intrigued to find that the expression of PD-L1 in non-tumor cells such as macrophages also predicted drug response,” said Herbst in an official statement.

The biopsies clearly provided a map of how subjects would respond to therapy based on functional and non-functional immune response via PD-L1 expression.

Of the 175 patients in the study, 21 percent showed either a partial or complete response to therapy with MPDL3280A and 46 percent of patients with strong PD-L1 expression in non-cancerous cells showed a partial or complete response to MPDL3280A. This was consistent across all types of tumors.

“We can begin learning how to use combination therapies to affect the immune response cycle,” said Herbst, who is currently involved in phase II and III trials for MPDL3280A.