{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:59:57Z","timestamp":1787774397380,"version":"build-2784847793"},"reference-count":59,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,7,24]]},"abstract":"<jats:sec>\n                  <jats:title>Abstract<\/jats:title>\n                  <jats:p>Emerging evidence indicates that CD4+ T cells contribute to antitumor immunity beyond their traditional roles as helpers or regulators. However, the specific subset of CD4+ T cells mediating beneficial outcomes in patients with multiple myeloma remains unclear. Here, we performed single-cell RNA sequencing and T-cell receptor sequencing on CD4+ T cells sorted from the bone marrow of patients across the stages of myeloma progression. We identified several distinct states of CD4+ cytotoxic T lymphocytes (CTLs) that were significantly increased and clonally expanded in patients with myeloma. CD4+ CTLs displayed transcriptional and phenotypic characteristics indicative of cytotoxicity, demonstrating their ability to directly kill myeloma cells. This cytotoxicity, however, was abrogated by NKG2D blockade. Notably, the abundance of NKG2D+CD4+ CTLs correlated with improved survival in patients with myeloma. Our findings suggest that harnessing CD4+ CTLs could lead to novel strategies for enhancing immunotherapy outcomes in multiple myeloma.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1182\/blood.2024025875","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T16:03:44Z","timestamp":1742400224000},"page":"456-470","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":8,"title":["NKG2D-mediated cytotoxicity of CD4 cytotoxic T cells in multiple myeloma"],"prefix":"10.1182","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1662-6855","authenticated-orcid":false,"given":"Sojeong","family":"Kim","sequence":"first","affiliation":[{"name":"1Blood Cancer Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea"},{"name":"2Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3178-0823","authenticated-orcid":false,"given":"Jeong-Eun","family":"Kwak","sequence":"additional","affiliation":[{"name":"1Blood Cancer Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea"},{"name":"2Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2043-6624","authenticated-orcid":false,"given":"June-Young","family":"Koh","sequence":"additional","affiliation":[{"name":"3Inocras Inc, San Diego, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3158-6709","authenticated-orcid":false,"given":"Ji Eun","family":"Lee","sequence":"additional","affiliation":[{"name":"1Blood Cancer Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea"},{"name":"2Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3544-0060","authenticated-orcid":false,"given":"Hye Won","family":"Kook","sequence":"additional","affiliation":[{"name":"1Blood Cancer Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea"},{"name":"2Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5017-4258","authenticated-orcid":false,"given":"Minchae","family":"Kim","sequence":"additional","affiliation":[{"name":"4Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7926-9285","authenticated-orcid":false,"given":"Haerim","family":"Chung","sequence":"additional","affiliation":[{"name":"1Blood Cancer Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea"},{"name":"2Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-0142","authenticated-orcid":false,"given":"Yu Ri","family":"Kim","sequence":"additional","affiliation":[{"name":"1Blood Cancer Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea"},{"name":"2Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8859-3573","authenticated-orcid":false,"given":"Soo Jeong","family":"Kim","sequence":"additional","affiliation":[{"name":"1Blood Cancer Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea"},{"name":"2Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8986-8436","authenticated-orcid":false,"given":"Jin Seok","family":"Kim","sequence":"additional","affiliation":[{"name":"1Blood Cancer Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea"},{"name":"2Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1744-0921","authenticated-orcid":false,"given":"June-Won","family":"Cheong","sequence":"additional","affiliation":[{"name":"1Blood Cancer Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea"},{"name":"2Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Goo","family":"Lee","sequence":"additional","affiliation":[{"name":"5Department of Pharmacology, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoyoung","family":"Lee","sequence":"additional","affiliation":[{"name":"6Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6363-7736","authenticated-orcid":false,"given":"Su-Hyung","family":"Park","sequence":"additional","affiliation":[{"name":"6Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6308-9503","authenticated-orcid":false,"given":"Eui-Cheol","family":"Shin","sequence":"additional","affiliation":[{"name":"6Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1501-3923","authenticated-orcid":false,"given":"Saeam","family":"Shin","sequence":"additional","affiliation":[{"name":"7Department of Laboratory Medicine, Yonsei University College of Medicine, 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