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The immunoglobulin superfamily ligand B7H6 subjects T cell responses to NK cell surveillance.
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.
Afiliação
  • Kilian M; DKTK Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Friedrich MJ; Department of Neurology, MCTN, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Lu KH; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Vonhören D; Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
  • Jansky S; DKTK Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Michel J; Department of Neurology, MCTN, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Keib A; Department of Pediatric Hematology and Oncology, Clinic of Pediatrics III, University Hospital Essen, Essen, Germany.
  • Stange S; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
  • Hackert N; Division of Neuroblastoma Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Kehl N; Department of Pediatric Hematology and Oncology, Clinic of Pediatrics III, University Hospital Essen, Essen, Germany.
  • Hahn M; Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.
  • Habel A; DKTK Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Jung S; Department of Neurology, MCTN, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Jähne K; Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
  • Sahm F; DKTK Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Betge J; Department of Neurology, MCTN, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Cerwenka A; Department of Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
  • Westermann F; DKTK Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Dreger P; Department of Neurology, MCTN, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Raab MS; DKTK Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Meindl-Beinker NM; Department of Neurology, MCTN, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Ebert M; Department of Neuropathology, Heidelberg University Hospital, Heidelberg, Germany.
  • Bunse L; DKTK Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Müller-Tidow C; Department of Neurology, MCTN, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Schmitt M; DKTK Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Platten M; Department of Neurology, MCTN, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Sci Immunol ; 9(95): eadj7970, 2024 May 03.
Article em En | MEDLINE | ID: mdl-38701193
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+ 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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Matadoras Naturais / Linfócitos T / Antígenos B7 Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Matadoras Naturais / Linfócitos T / Antígenos B7 Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article