Session: 651. Multiple Myeloma and Plasma Cell Dyscrasias: Basic and Translational: Poster I
Hematology Disease Topics & Pathways:
Diversity, Equity, and Inclusion (DEI) , immunology, Biological Processes
Methods: The iTME was characterized in 51 viably frozen whole bone marrow (BM) aspirates obtained from 21 AA and 30 NHW individuals. Of the 21 BM samples from AA individuals, 15 had MM, 2 had SMM and 4 had MGUS. Of the 30 BM samples from NHW individuals, 24 had MM, 1 had SMM and 5 had MGUS. The frozen specimens were thawed, washed using warmed cell culture media containing benzonase nuclease, stained using the Maxper Direct Immune Profiling Assay Kit (Fluidigm), fixed, and washed according to the manufacturer’s guidelines. Data were acquired with a Helios mass cytometer. A total of 32 immune cell populations were analyzed by the Cytobank software. All statistical analyses were performed using GraphPad Prism and BlueSky Statistics. A Student’s t-test/Mann-Whitney U test was used to compare two independent groups. All tests were two-tailed and an FDR-adjusted p<0.05 was considered significant.
Results: Of the 32 immune cell populations analyzed, significant differences in the abundance of 13 immune populations between AA (median age 61 yrs) and NHW (median age 66 yrs) individuals with MM were identified. In relation to the CD45+CD66b- lymphocyte population, we found greater total mean CD3+ T cells (AA 52.3% vs. NHW 37.9%, p<0.001) including a greater mean CD4+ T cells (AA 24.0% vs. NHW 18.9%, p<0.05) and a greater mean CD8+ T cells (AA 22.7% vs. NHW 14.4%, p<0.05), CD4+ terminal effector cells (AA 7.0% vs. NHW 3.7%, p<0.001) and a greater mean CD8+ terminal effector cells (AA 13.8% vs. NHW 7.1%, p<0.05), CD4+ naïve (AA 2.4% vs. NHW 4.3%, p<0.05) and effector memory (AA 8.1% vs. NHW 5.3%, p<0.05), Th1-like (AA 0.7% vs. NHW 0.3%, p<0.05) and gamma delta T cells (AA 1.1% vs. NHW 0.5%, p<0.05) in AA compared to NHW patients with MM. Significant reductions in the mean basophils (AA 0.1% vs. NHW 0.3%, p<0.05) and monocytes (AA 18.4% vs. NHW 29.8%, p<0.01) were also observed in AA compared to NHW patients with MM. Since CD8+ T cell-mediated anti-myeloma response has been demonstrated in mouse models, which suggested a critical role for CD8+ T cells as dominant effectors of MM cell death, we focused our analysis on the CD8+ T cell population. Of the CD8+ terminal effector T cells, we observed an enrichment of CD28-CD57+ CD8+ “senescent T cells”, a highly cytotoxic but terminally differentiated T cell state, with diminished proliferative capacity in AA compared to NHW patients (AA 43.6% vs. NHW 25.5%, p<0.05). Conversely, AA patients also had decreased CD28+CD57- CD8+ T cells (AA 30.3% vs. NHW 44.2%, p<0.05). Further, MM patients with high senescent CD8+ T cells (>30%) had a favorable overall survival compared to patients with low senescent CD8+ T cells (<30%) (HR 0.26, 95% CI 0.07-1, p-value 0.037).
Conclusion: The T cell lineage displays the most significant difference in the immune cell composition between AA and NHW patients with MM. Additional studies are necessary to determine whether the increased cytotoxic T cells, which may have expanded in response to tumor antigens, explain the improved outcomes of AA patients with MM.
Disclosures: Kourelis: Novartis: Research Funding. Kumar: Roche: Research Funding; Novartis,: Research Funding; Merck,: Research Funding; MedImmune/Astra Zeneca,: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE,: Research Funding; Adaptive,: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda,: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen,: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie,: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Oncopeptides: Other: Independent review committee. Baughn: Roche-Genentech: Consultancy.
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