Immunotherapies harness a patient's own immune system to target and destroy cancer cells. One type of immunotherapy, immune checkpoint inhibitors, blocks the mechanisms that cancer cells use to hide from the immune system, leaving tumors vulnerable to attack by cytotoxic T cells. Drugs targeting the immune checkpoint receptor PD-1 and its ligand, PD-L1, have been shown to successfully activate T cells against certain cancers, but their efficacy varies between cancer types and between individual patients. In this week's issue of the JCI, a collaboration between David Raulet's laboratory at UC Berkley and Michele Ardolino's laboratory at the University of Ottawa uncovers an important role for a different type of immune cell in PD-1/PD-L1-targeting immunotherapy, a discovery that may help scientists develop more powerful immune-targeting anti-cancer treatments.
Research conducted by Joy Hsu, Jonathan Hodgkins, and colleagues examined how natural killer (NK) cells within tumors respond to PD-1/PD-L1 blockade in mouse models of cancer. Like T cells, NK cells are capable of killing cells, although their cytotoxic functions differ. Here, the researchers identified a subpopulation of PD-1-expressing NK cells that reside exclusively within tumors. In models of cancer where PD-1/PD-L1 blockade failed to activate T cells against tumors, these NK cells were capable of targeting the tumor. Similarly, in tumors depleted of T cells, PD-1/PD-L1 blockade retained anti-cancer effects as long as NK cells were present.
The study's findings suggest that these intratumoral NK cells are capable of contributing to the efficacy of checkpoint blockade anti-cancer therapies. Cordelia Dunai and William Murphy highlight this study's importance in an accompanying commentary and indicate that more research into this type of NK cell could lead to strategies that exploit its role to improve checkpoint-targeting immunotherapies for cancer.
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TITLE: Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade
AUTHOR CONTACT: David H Raulet
Email: raulet@berkeley.edu
View this article at: https://www.jci.org/articles/view/99317?key=c9f7c26b57c88cada531
ACCOMPANYING COMMENTARY: https://www.jci.org/articles/view/123121?key=ef0321bb5cdd827057e3
Journal
Journal of Clinical Investigation