Abstract B177: Analysis of immunogenic cell death (ICD) induced in multiple myeloma cells

Background: Development of novel drugs, such as immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), or monoclonal antibodies, has prolonged survival of multiple myeloma (MM) patients. However, high-risk patients harboring del 17, t(14;17), or t(11;14) still have poor prognosis. Therefore, clarification of the drugs that could potentiate the effect of these treatments is necessary. Several drugs have been reported to cause cell surface expression of calreticulin (CRT), release of high mobility group box 1 (HMGB 1) and ATP, activating an immune response, which is called immunogenic cell death (ICD). However, there is almost no information on ICD in MM. The purpose of this study is to investigate whether anti-MM drugs can induce not only direct cell-killing effect but also immunomodulatory effects in high-risk MM cells. Methods: High-risk myeloma cell line, MUM24 was treated with dexamethasone, melphalan, lenalidomide, bortezomib, carfilzomib, and panobinostat. Expression of cell surface CRT and HMGB1 release were detected using flow cytometry and Western blotting, respectively. We then co-cultured DiD-labeled monocyte-derived dendritic cells with GFP-induced MUM24 treated with each drug and evaluated phagocytosis of DCs using fluorescence microscope. Results: After treatment with drugs, bortezomib and carfilzomib induced higher expression of CRT and release of HMGB1 in MUM24 compared with other drugs. We also observed that DCs could engulf MUM24 cells treated with carfilzomib. Conclusion: Our results suggest that PIs, such as bortezomib or carfilzomib, could not only kill MM cells but also induce ICD. These effects are expected to improve the prognosis of MM patients by evoking strong immune response against MM cells. Citation Format: Maiko Matsushita, Sho Kashiwazaki, Satoshi Kamiko, Ryo Uozaki, Daiju Ichikawa, Yutaka Hattori. Analysis of immunogenic cell death (ICD) induced in multiple myeloma cells [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B177.