{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:20:43Z","timestamp":1790266843131,"version":"4.1.0"},"reference-count":35,"publisher":"American Society of Hematology","issue":"12","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,3,21]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>The CD161 inhibitory receptor is highly upregulated by tumor-infiltrating T cells in multiple human solid tumor types, and its ligand, CLEC2D, is expressed by both tumor cells and infiltrating myeloid cells. Here, we assessed the role of the CD161 receptor in hematological malignancies. Systematic analysis of CLEC2D expression using the Cancer Cell Line Encyclopedia revealed that CLEC2D messenger RNA was most abundant in hematological malignancies, including B-cell and T-cell lymphomas as well as lymphocytic and myelogenous leukemias. CLEC2D protein was detected by flow cytometry on a panel of cell lines representing a diverse set of hematological malignancies. We, therefore, used yeast display to generate a panel of high-affinity, fully human CD161 monoclonal antibodies (mAbs) that blocked CLEC2D binding. These mAbs were specific for CD161 and had a similar affinity for human and nonhuman primate CD161, a property relevant for clinical translation. A high-affinity CD161 mAb enhanced key aspects of T-cell function, including cytotoxicity, cytokine production, and proliferation, against B-cell lines originating from patients with acute lymphoblastic leukemia, diffuse large B-cell lymphoma, and Burkitt lymphoma. In humanized mouse models, this CD161 mAb enhanced T-cell\u2013mediated immunity, resulting in a significant survival benefit. Single cell RNA-seq data demonstrated that CD161 mAb treatment enhanced expression of cytotoxicity genes by CD4 T cells as well as a tissue-residency program by CD4 and CD8 T cells that is associated with favorable survival outcomes in multiple human cancer types. These fully human mAbs, thus, represent potential immunotherapy agents for hematological malignancies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2023022882","type":"journal-article","created":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T13:17:46Z","timestamp":1703769466000},"page":"1124-1138","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":25,"title":["Targeting of the CD161 inhibitory receptor enhances T-cell\u2013mediated immunity against hematological malignancies"],"prefix":"10.1182","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5620-8431","authenticated-orcid":false,"given":"Francesca","family":"Alvarez Calderon","sequence":"first","affiliation":[{"name":"1Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA"},{"name":"2Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA"},{"name":"3Division of Hematology\/Oncology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA"},{"name":"4Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1637-2082","authenticated-orcid":false,"given":"Byong H.","family":"Kang","sequence":"additional","affiliation":[{"name":"5Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA"},{"name":"6Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7646-6363","authenticated-orcid":false,"given":"Oleksandr","family":"Kyrysyuk","sequence":"additional","affiliation":[{"name":"1Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6682-6743","authenticated-orcid":false,"given":"Shiwei","family":"Zheng","sequence":"additional","affiliation":[{"name":"7Department of Genetics and Genomic Sciences, Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8729-8556","authenticated-orcid":false,"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"1Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA"},{"name":"8Department of Immunology, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8895-2609","authenticated-orcid":false,"given":"Nathan 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