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Defining pDC-MM interaction-triggered immunosuppressive mechanism(s) will enable design of interventional therapies to augment anti-MM immunity. In the present study, we show that pDC-MM interactions induce metabolic enzyme Ecto-5' Nucleotidase\/CD73 in both pDCs and MM cells. Gene expression database from MM patients showed that <jats:italic>CD73<\/jats:italic> levels inversely correlate with overall survival. Using our pDC-MM coculture models, we found that blockade of CD73 with anti-CD73 Abs: decreases adenosine levels; activates MM patient pDCs; triggers cytotoxic T lymphocytes (CTL) activity against autologous patient MM cells. Combination of anti-CD73 Abs and an immune-stimulating agent TLR-7 agonist enhances autologous MM-specific CD8<jats:sup><jats:bold>+<\/jats:bold><\/jats:sup> CTL activity. Taken together, our preclinical data suggest that the therapeutic targeting of CD73, alone or in combination with TLR-7 agonist, represents a promising novel strategy to restore host anti-MM immunity.<\/jats:p>","DOI":"10.1038\/s41408-022-00635-3","type":"journal-article","created":{"date-parts":[[2022,4,1]],"date-time":"2022-04-01T10:22:14Z","timestamp":1648808534000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Identification and validation of ecto-5' nucleotidase as an immunotherapeutic target in multiple myeloma"],"prefix":"10.1038","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0652-2905","authenticated-orcid":false,"given":"Arghya","family":"Ray","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6729-2672","authenticated-orcid":false,"given":"Yan","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leutz","family":"Buon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6199-3569","authenticated-orcid":false,"given":"Yu-Tzu","family":"Tai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5548-6138","authenticated-orcid":false,"given":"Dharminder","family":"Chauhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6418-0886","authenticated-orcid":false,"given":"Kenneth C.","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,1]]},"reference":[{"key":"635_CR1","doi-asserted-by":"publisher","first-page":"17046","DOI":"10.1038\/nrdp.2017.46","volume":"3","author":"SK Kumar","year":"2017","unstructured":"Kumar SK, Rajkumar V, Kyle RA, van Duin M, Sonneveld P, Mateos MV, et al. 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DC is a consultant to Stemline Therapeutic, Inc., and equity owner in C4 Therapeutics. Other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"50"}}