COLUMBUS, Ohio – New laboratory findings from The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) reveal that some white blood cells that would normally target and kill tumor cells might become molecularly hijacked in certain scenarios, working against the body’s ability to fight cancer. Blocking these cells to let the targeted immunotherapy take over then attack cancer cells could improve treatment effectiveness. In this Pelotonia Institute for Immuno-Oncology (PIIO)-led study, researchers aimed to understand how certain immune cells – known as natural killer (NK) cells – affect the effectiveness of immune checkpoint treatment for cancers. These treatments help the body's immune system fight cancer by targeting a pathway (PD-1/PD-L) involved in cancer’s development and spread. The researchers wanted to see if removing NK cells could improve the treatment's success. PDL-1 (programmed death-ligand 1) is a protein found on some cancer cells that helps them avoid the body’s immune system by interacting with another protein called PD-1. Drugs that block this interaction are used to treat non-small cell lung cancer as well as melanoma, liver cancer, breast cancer, urothelial carcinoma, and some head and neck cancers. “We discovered that some NK cells in tumors actually make it harder for another type of immune cell, called CD8+ T cells, to fight cancer. These NK cells compete with CD8+ T cells for important proteins called cytokines, which are needed for the T cells to work properly,” said the first author No Joon Song, PhD, a postdoctoral scholar in the lab of PIIO founding director and study senior author Zihai Li, MD, PhD. Although NK cells are conventionally considered as a beneficial immune cell population, when NK cells were removed, explained Song, a new type of CD8+ T cells emerged which are far better able to fight the cancer. These cells, called NK regulated T cells (NKRTs), had a unique set of markers that made them more effective. “This suggests this approach to treatment could lead to smaller tumors and result in better overall treatment results,” said Song. Li believes that the important discovery of NKRTs could open the way for future treatments. “Targeting NK cells in the tumor specifically could lead to improvement of the effectiveness of CD8+ T cell-based cancer therapies in the clinic. More intriguingly, other approaches to unleash NKRTs could open new therapeutic avenues,” said Li. The team will conduct more research to further understand how NK cells and CD8+ T cells interact, and how this knowledge can be used to develop better cancer treatments. Findings were published in the medical journal Cancer Discovery. Coauthors in this study include Juan Xie, Kyeong Joo Jung, Yi Wang, Brian Riesenberg, Hyeongseon Jeon, Anjun Ma, Nathaneal Cox, Darren Wethington, Kelsi Reynolds, Tong Xiao, Anqi Li, Parker Ronen, Nicholas Denko, David Carbone, Qin Ma, William Carson III, Bethany Mundy-Bosse, Christin Burd, Jayajit Das and Dongjun Chung of the OSUCCC – James, and Joanna Pozniak, Niccola Roda and Jean-Christophe Marine of the Center Laboratory of Molecular Cancer Biology in Belgium. This study was supported by the PIIO, National Institutes of Health and American Cancer Society. ### MEDIA CONTACT: Amanda Harper amanda.harper2@osumc.edu | 614-685-5420 cancer.osu.edu/news