Ray, ArghyaSong, YanDu, TingBuon, LeutzTai, Yu-TzuChauhan, DharminderAnderson, Kenneth2022-08-262022-04-01Ray, Arghya, Yan Song, Ting Du, Leutz Buon, Yu-Tzu Tai, Dharminder Chauhan, and Kenneth C Anderson. 2022. “Identification and Validation of Ecto-5' Nucleotidase as an Immunotherapeutic Target in Multiple Myeloma.” Blood Cancer Journal (New York) 12 (4): 50.2044-5385https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37373076Interaction of plasmacytoid dendritic cells (pDCs) with multiple myeloma (MM) cells, T- or NK-effector cells in the bone marrow (BM) microenvironment induces tumor cell growth, as well as inhibits innate and adaptive immune responses. 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 CD73 levels inversely correlates 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; and 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+ 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.en-USOncologyHematologyJournal Article2022-08-2610.1038/s41408-022-00635-3