Mechanism Behind NK Control of T Cells Identified

Researchers from the German Cancer Research Center and University Medical Center Mannheim have discovered that natural killer (NK) cells can impair the effectiveness of cancer immunotherapies by controlling activated T cells. T cells are crucial for fighting infections and cancer, but their activity must be tightly regulated to prevent autoimmune reactions.

The study, published in Science Immunology, found that NK cells can recognize and kill activated T cells expressing the protein B7H6 on their surface. This appears to be a mechanism for limiting excessive T cell activation and proliferation. While beneficial for curbing autoimmunity, it can counteract cancer immunotherapies that rely on activating tumor-targeting T cells.

For patients with esophageal cancer treated with immune checkpoint inhibitor (ICI) therapy, those who did not respond had higher levels of NK cells in their tumors and shorter progression-free survival. This suggests NK cell elimination of the therapy-activated T cells reduced treatment efficacy.

The researchers also examined cellular immunotherapies like CAR-T cells, which are engineered T cells designed to target cancer. These therapeutic cells also express B7H6, making them susceptible to NK cell killing. In a humanized mouse model of leukemia, adding NK cells decreased CAR-T cell numbers and increased tumor burden.

The authors conclude that NK cell control of T cells has the potential to interfere with various cancer immunotherapies. By modulating this process, it may be possible to enhance T cell responses against tumors. They plan to use CRISPR gene editing to protect CAR-T cells from NK cell elimination in an upcoming clinical trial, aiming to improve the effectiveness of this cellular immunotherapy.