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We previously reported that CD34<jats:sup>+<\/jats:sup> MM cells, which are clonogenic and self-renewing, are therapy-resistant and persist as a major component of minimal residual disease, expanding during relapse. To investigate the effects of immunotherapies such as immune-checkpoint inhibitors, CAR-T therapy, and bispecific antibodies on CD34<jats:sup>+<\/jats:sup> MM cells, we analyzed immune profiles of both MM cells and T cells from MM patients using microarrays and flow cytometry. Ingenuity pathway analysis revealed 14 out of 289 canonical pathways were more active in CD34<jats:sup>+<\/jats:sup> MM cells compared to CD34<jats:sup>\u2212<\/jats:sup> cells, many of which were involved in inflammation and immune responses. Notably, PD-1 signaling-related genes were highly expressed in CD34<jats:sup>+<\/jats:sup> MM cells. Among 10 immune-checkpoint molecules, CD34<jats:sup>+<\/jats:sup> cells more frequently expressed CD112, CD137L, CD270, CD275, and GAL9 than CD34<jats:sup>\u2212<\/jats:sup> cells in both newly diagnosed and relapsed\/resistant patients. In addition, CD4<jats:sup>+<\/jats:sup> and CD8<jats:sup>+<\/jats:sup> T cells more frequently expressed TIGIT and CD137, suggesting that CD112\/TIGIT and CD137L\/CD137 interactions may suppress T-cell activity against CD34<jats:sup>+<\/jats:sup> MM cells. Furthermore, our finding of higher FcRH5 expression on CD34<jats:sup>+<\/jats:sup> MM cells is encouraging for future research into the efficacy of FcRH5-targeted therapy in MM.<\/jats:p>","DOI":"10.1007\/s12185-024-03867-0","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T05:38:40Z","timestamp":1731389920000},"page":"89-99","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CD34+ and CD34\u2212 MM cells show different immune-checkpoint molecule expression profiles: high expression of CD112 and CD137 ligand on CD34+ MM cells"],"prefix":"10.1007","volume":"121","author":[{"given":"Ayano","family":"Fukui-Morimoto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Serizawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ko","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aki","family":"Hanamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshio","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Kakutani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Kumode","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chikara","family":"Hirase","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuyoshi","family":"Morita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoichi","family":"Tatsumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Hanamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirokazu","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Itaru","family":"Matsumura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,11,12]]},"reference":[{"issue":"10272","key":"3867_CR1","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/S0140-6736(21)00135-5","volume":"397","author":"NWCJ van de Donk","year":"2021","unstructured":"van de Donk NWCJ, Pawlyn C, Yong KL. 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Y.M. received personal fees from AbbVie GK, NIPPON SHINYAKU CO., LTD., and Alexion Pharmaceuticals, Inc. H.H. received personal fees from Pfizer Japan Inc., CSL Behring, and Takeda Pharmaceutical Company Limited. H.T. received grants from JSPS KAKENHI, ONO PHARMACEUTICAL CO., LTD., and Kyowa Kirin Co., Ltd.; personal fees from Bristol-Myers Squibb (Celgene), Novartis Pharmaceuticals, ONO PHARMACEUTICAL CO., LTD., Janssen Pharmaceutical K.K, Takeda Pharmaceutical Company Limited., Sanofi, Meiji Seika Pharma Co., Ltd., Otsuka Pharmaceutical Co., Ltd., and Adaptive Biotechnologies. S.R. received personal fees from Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Bristol-Myers Squibb (Celgene), Janssen Pharmaceutical K.K, Takeda Pharmaceutical Company Limited., and Amgen BioPharma K.K., and Mundipharma K.K. I.M. received grants from ONO PHARMACEUTICAL CO., LTD., NIPPON SHINYAKU CO., LTD., Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Shionogi & Co., Ltd., TEIJIN PHARMA LIMITED., Boehringer Ingelheim, Sanofi, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., MSD K.K, ASAHI KASEI PHARMA CORPORATION, Astellas Pharma Inc., Takeda Pharmaceutical Company Limited., Japan Blood Products Organization, NIHON PHARMACEUTICAL CO., LTD, DAIICHI SANKYO COMPANY, TAIHO PHARMACEUTICAL CO., LTD., Mitsubishi Tanabe Pharma Corporation, Nippon Kayaku Co.,Ltd., CSL Behring, Mundipharma K.K, AYUMI Pharmaceutical Corporation, Eli Lilly Japan K.K., and Actelion Pharmaceuticals Japan Ltd.,; personal fees from Bristol-Myers Squibb (Celgene), Novartis Pharmaceuticals, ONO PHARMACEUTICAL CO., LTD., Janssen Pharmaceutical K.K, NIPPON SHINYAKU CO.,LTD., Shionogi & Co., Ltd., Astellas Pharma Inc., Takeda Pharmaceutical Company Limited., DAIICHI SANKYO COMPANY, AbbVie GK, and Amgen BioPharma K.K. The remaining authors declare no competing financial interests. The remaining authors declare no competing financial interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All samples were collected after obtaining the approval of the ethics committee of our institute (Authorization Number: 24-017, -018) and the written informed consent from the patients. This study was conducted according to the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}