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The immunoglobulin superfamily ligand B7H6 subjects T cell responses to NK cell surveillance.
- Source :
- Science Immunology; 2024, Vol. 9 Issue 95, p1-13, 13p
- Publication Year :
- 2024
-
Abstract
- Understanding the mechanisms that regulate T cell immunity is critical for the development of effective therapies for diseases associated with T cell dysfunction, including autoimmune diseases, chronic infections, and cancer. Co-inhibitory "checkpoint molecules," such as programmed cell death protein-1, balance excessive or prolonged immune activation by T cell–intrinsic signaling. Here, by screening for mediators of natural killer (NK) cell recognition on T cells, we identified the immunoglobulin superfamily ligand B7H6 to be highly expressed by activated T cells, including patient-infused CD19-targeting chimeric antigen receptor (CAR) T cells. Unlike other checkpoint molecules, B7H6 mediated NKp30-dependent recognition and subsequent cytolysis of activated T cells by NK cells. B7H6<superscript>+</superscript> T cells were prevalent in the tissue and blood of several diseases, and their abundance in tumor tissue positively correlated with clinical response in a cohort of patients with immune checkpoint inhibitor–treated esophageal cancer. In humanized mouse models, NK cell surveillance via B7H6 limited the persistence and antitumor activity of CAR T cells, and its genetic deletion enhanced T cell proliferation and persistence. Together, we provide evidence of B7H6 protein expression by activated T cells and suggest the B7H6-NKp30 axis as a therapeutically actionable NK cell–dependent immune checkpoint that regulates human T cell function. Editor's summary: Natural killer (NK) cells can eliminate infected or malignant cells, but they are also believed to be capable of killing host immune cells. By screening NK cell ligands on human T cells, Kilian et al. found that the immunoglobulin superfamily ligand B7H6 promotes cytolysis of activated T cells by NK cells. In leukemia-bearing humanized mice, NK cells restricted the antitumor activity of chimeric antigen receptor (CAR) T cells in a B7H6-dependent manner. A higher ratio of intratumoral NK to T cells was associated with poor response to immune checkpoint inhibition in a cohort of patients with esophageal cancer. These findings demonstrate that B7H6 recognition by NK cells can restrict human antitumor T cell responses. —Claire Olingy [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 24709468
- Volume :
- 9
- Issue :
- 95
- Database :
- Complementary Index
- Journal :
- Science Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 177778654
- Full Text :
- https://doi.org/10.1126/sciimmunol.adj7970