Details

Autor(en) / Beteiligte

• Kilian, Michael
• Friedrich, Mirco J
• Lu, Kevin Hai-Ning
• Vonhören, David
• Jansky, Selina
• Michel, Julius
• Keib, Anna
• Stange, Saskia
• Hackert, Nicolaj
• Kehl, Niklas
• Hahn, Markus
• Habel, Antje
• Jung, Stefanie
• Jähne, Kristine
• Sahm, Felix
• Betge, Johannes
• Cerwenka, Adelheid
• Westermann, Frank
• Dreger, Peter
• Raab, Marc S
• Meindl-Beinker, Nadja M
• Ebert, Matthias
• Bunse, Lukas
• Müller-Tidow, Carsten
• Schmitt, Michael
• Platten, Michael

Titel

The immunoglobulin superfamily ligand B7H6 subjects T cell responses to NK cell surveillance

Ist Teil von

• Science immunology, 2024-05, Vol.9 (95), p.eadj7970

Ort / Verlag

United States

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 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.