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Talk by Dominika Nowis

Title: "The role of arginases, myeloid cells, and CECs (CD71+ erythroid progenitor and precursor cells) in the progression of multiple myeloma"
Occasion: SFB - Seminar
Start: 28.05.2025 4:15 pm
Location: CellNanOs, 38/201

About the speaker: Dr. Dominika Nowis conducts research at the Medical University, Warsaw

Multiple myeloma (MM) remains an incurable malignancy of plasma cells despite constantly evolving therapeutic approaches including various types of immunotherapy. Increased arginase activity has been associated with potent suppression of T-cell immune responses in various types of cancer. Here, we investigated the role of arginases (ARG1 & ARG2) in Vκ*MYC model of multiple myeloma in mice – in the regulation of antigen-specific immune responses as well as in the bacterial infections control. ARGs expression in myeloid cells as well as in the CD71+ erythroid progenitor and precursor cells (CECs) correlated with tumor progression and was accompanied by a systemic decrease in ʟ-arginine levels. In MM-bearing mice antigen-induced proliferation of adoptively transferred T-cells was strongly suppressed and T-cell proliferation was restored by pharmacological arginase inhibition. Progression of Vκ*MYC tumors was significantly delayed in mice with myeloid-specific ARG1 deletion as well as in mice lacking functional ARG2 in all tissues. We have also observed increased percentage of CECs in the bone marrow of MM patients and enhanced expression of both ARG1 and ARG2 in these cells. Moreover, MM-associated CECs inhibited proliferation of human T-cells in both ARG- and reactive oxygen species-dependent manner. Arginase inhibition was ineffective in inhibiting tumor progression and did not augment anti-myeloma effects of bortezomib. However, it prevented development of bortezomib-induced cardiotoxicity and decreased disease load in L. monocytogenes – infected Vκ*MYC-bearing mice. Altogether, these findings indicate that arginases impair development of effective immune responses and inhibitors of these enzymes could be further tested as a complementary strategy in multiple myeloma to: i) mitigate adverse cardiac events without compromising antitumor efficacy of proteasome inhibitors, ii) improve bacterial infection control in MM patients.