Study sheds light on some tumors’ ability to evade a promising immunotherapy strategy

In the last decade, cancer immunotherapies have demonstrated improved clinical outcomes in patients with a variety of cancers. However, only a small subset of patients respond to the treatment, known as PD-1/PD-L1 blockade. A new paper, published in Nature Cell Biology, sheds light on the mechanisms underlying tumors’ ability to evade PD-1-mediated immune surveillance.

Wenyi Wei, PhD, a Professor in the Department of Pathology and a member of the Cancer Research Institute at Beth Israel Deaconess Medical Center (BIDMC), and colleagues — including first author, Yang Gao, MD, PhD, a research fellow in BIDMC’s Department of Pathology, co-corresponding authors Gordon Freeman, PhD, and Piotr Sicinski, MD, PhD, of Dana-Farber Cancer Institute and Yoshio Miki, MD, PhD, of Tokyo Dental and Medical University — explored on the regulatory pathways of PD-L1, a molecule known to help cancer cells evade the immune system. The researchers revealed the complex biochemical pathway by which PD-L1, a known membrane-anchored molecule, can translocate to the tumor cell’s nucleus. Once there, PD-L1 regulates multiple immune-related genes, thus modifying the anti-tumor immune response. Though further study will be necessary, the findings suggest a strategy for improving cancer immunotherapy treatments.

“Although PD-1 blockade has been proven to be clinically effective in treating various human cancers, fewer than a third of patients respond positively,” said Wei. “It is critically important to understand how to turn the majority of tumors that will better respond to this promising form of cancer immunotherapy.”

Please see the publication for the full list of authors, funders and financial disclosures.

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