84P Microenvironment immune differences between sexes in multiple myeloma

Several studies showed that sex is a biological variable that influence immune response in several types of solid tumors; however, there is scarce information in hematological malignancies. In this work, we evaluate differences in immune cells compositions and immune response of multiple myeloma between sexes. We conducted a computational biology study using transcriptomic data obtained from bone marrow aspiration collected from untreated multiple myeloma patients under the MMRF-COMMPASS protocol (study accession phs000748). Data was pre-processed and the expression levels were normalized to TPM (transcript per million). To evaluate differences in immune cells compositions, we quantified the immune cell in the tumor microenvironment with the analytic platform CIBERSORT. Differences in activated immune pathways was evaluated with the gene set enrichment analysis (GSEA). Pre-processed counts were normalized to TMM (trimmed mean of M-values) and GSEA was performed using the GSEA java desktop application (v4.3.2). In both analysis, patterns of immune gene sets and the immune cell composition were compared between tumors from female vs. male patients. A p<0.05 and a FDR<25% were considered statistically significant for GSEA analysis, while a p<0.05 and a FDR<0.05 6.1x10-5 was considered statistically significant for CIBERSORT analysis. Overall, 451 males and 313 female patients were included. We detected in samples from female patients an enrichment of dendritic cells activated (p=0.0023, FDR=0,0257) and NK cells activated (p=0.0059, FDR=0,0326). In contrast, we observed in male patients an enrichment of monocytes (p=6.10x 10-5, FDR=0,0013) and macrophages M1(p=0,0050, FDR=0,0326). The GSEA analysis revealed an overregulation of natural killer cell degranulation (p=0.007, FDR=0.21624), positive regulation of type I interferon mediated signaling pathway (p<0.0001, FDR=0.23946), and regulation of natural killer cell proliferation (p=0.01, FDR=0.2495). The computational analysis showed some differences in the immune microenvironment, between sexes in multiple myeloma. Studies about the influence of these differences in the clinical outcomes of patients should be evaluated.