{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T01:52:05Z","timestamp":1793065925559,"version":"4.5.0"},"reference-count":74,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T00:00:00Z","timestamp":1704672000000},"content-version":"unspecified","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008005","name":"Yonsei University College of Medicine","doi-asserted-by":"publisher","award":["6-2021-0101"],"award-info":[{"award-number":["6-2021-0101"]}],"id":[{"id":"10.13039\/501100008005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"crossref","award":["HI22C1217"],"award-info":[{"award-number":["HI22C1217"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"crossref","award":["HI22C1826"],"award-info":[{"award-number":["HI22C1826"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ministry of Science and ICT, Republic of Korea","award":["RS-2023-00208390"],"award-info":[{"award-number":["RS-2023-00208390"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2023,11,28]]},"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Major histocompatibility complex (MHC) class I chain-related protein (MIC) is a stress-induced ligand released from multiple myeloma (MM) cells during progression, and soluble MIC impairs natural killer group 2D (NKG2D) activating receptor-mediated recognition and function of natural killer (NK) cells. However, whether clearing soluble MIC with a monoclonal antibody (mAb) can restore NK cell activity of MM patients remains undetermined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed The Cancer Genome Atlas (TCGA) Multiple Myeloma Research Foundation (MMRF) CoMMpass data set to examine the prognostic significance of\n                      <jats:italic>MIC<\/jats:italic>\n                      expression in MM. We examined the level of soluble MIC in paired peripheral blood (PB) and bone marrow (BM) plasma of patients with MM at diagnosis by ELISA. We evaluated the correlation between the level of soluble MIC and immunophenotype of NK cells from MM patients by multicolor flow cytometry. We also generated MIC-overexpressing MM cell line and characterized the cytotoxic function of patient NK cells in the presence of soluble MIC, and examined the impact of clearing soluble MIC with a humanized mAb (huB10G5).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We characterize the importance of MICA in MM by revealing the significantly better overall survival of patients with high\n                      <jats:italic>MICA<\/jats:italic>\n                      expression from TCGA MMRF CoMMpass data set. The level of soluble MICA is more highly elevated in MM than in precursor stages, and the concentration of soluble MICA is higher in BM plasma than in PB. The concentration of soluble MICA in BM was correlated with myeloma burden, while it was negatively correlated with the frequency of NKG2D\n                      <jats:sup>+<\/jats:sup>\n                      NK cells in diagnostic BM aspirates of MM patients. Soluble MICA downregulated NKG2D expression and decreased cytotoxicity of MM patient NK cells\n                      <jats:italic>ex vivo<\/jats:italic>\n                      , which were reversed by a humanized soluble MIC-clearing mAb (huB10G5) with enhanced degranulation of NK cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings indicate targeting soluble MIC with huB10G5 might be a viable therapeutic approach to promote NKG2D-dependent cellular immunotherapy outcome in MM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2023-007886","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T01:02:43Z","timestamp":1704848563000},"page":"e007886","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Clearing soluble MIC reverses the impaired function of natural killer cells from patients with multiple myeloma"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct01454297","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01454297","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Sojeong","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haerim","family":"Chung","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (the Republic of)"}],"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":"Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Ri","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung Hyun","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeonhee","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"June-Won","family":"Cheong","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Urology and Department of Microbiology and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA"}],"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":"Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2651-6403","authenticated-orcid":false,"given":"Hyunsoo","family":"Cho","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Seok","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (the Republic of)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2024,1,8]]},"reference":[{"key":"2025100303252310000_12.1.e007886.1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(21)00135-5"},{"key":"2025100303252310000_12.1.e007886.2","doi-asserted-by":"crossref","first-page":"2358","DOI":"10.3324\/haematol.2020.247015","article-title":"Multiple myeloma: the (R)Evolution of current therapy and a glance into future","volume":"105","author":"Gulla","year":"2020","journal-title":"Haematologica"},{"key":"2025100303252310000_12.1.e007886.3","doi-asserted-by":"crossref","DOI":"10.1186\/s13045-022-01296-2","article-title":"Patient selection for CAR T or bite therapy in multiple myeloma: which treatment for each patient","volume":"15","author":"Kegyes","year":"2022","journal-title":"J Hematol Oncol"},{"key":"2025100303252310000_12.1.e007886.4","first-page":"275","article-title":"Chimeric antigen receptor T-cell therapy in multiple myeloma: A comprehensive review of current data and implications for clinical practice","volume":"73","author":"Parikh","year":"2023","journal-title":"CA Cancer J Clin"},{"key":"2025100303252310000_12.1.e007886.5","doi-asserted-by":"crossref","DOI":"10.1038\/s41408-020-0273-x","article-title":"Developments in continuous therapy and maintenance treatment approaches for patients with newly diagnosed multiple myeloma","volume":"10","author":"Dimopoulos","year":"2020","journal-title":"Blood Cancer J"},{"key":"2025100303252310000_12.1.e007886.6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41409-020-01023-w","article-title":"Chimeric antigen receptor T cell therapy in multiple myeloma: promise and challenges","volume":"56","author":"Dhakal","year":"2021","journal-title":"Bone Marrow Transplant"},{"key":"2025100303252310000_12.1.e007886.7","doi-asserted-by":"crossref","DOI":"10.1038\/s41408-021-00469-5","article-title":"CAR T-cell therapy in multiple myeloma: more room for 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Antibody targeting tumor-derived soluble Nkg2D ligand sMIC provides dual Co-stimulation of Cd8 T cells and enables sMIC(+) tumors respond to Pd1\/PD-L1 blockade therapy. 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