CD84 is a regulator of the immunosuppressive microenvironment in multiple myeloma.

Multiple myeloma (MM) is characterized by an accumulation of malignant plasma cells (PCs) within the BM. The BM microenvironment supports survival of the malignant cells and is composed of cellular fractions that foster myeloma development and progression by suppression of the immune response. Despite major progress in understanding the biology and pathophysiology of MM, this disease is still incurable and requires aggressive treatment with significant side effects. CD84 is a self-binding immunoreceptor belonging to the signaling lymphocyte activation molecule (SLAM) family. Previously, we showed that CD84 bridges between chronic lymphocytic leukemia cells and their microenvironment, and it regulates T cell function. In the current study, we investigated the role of CD84 in MM. Our results show that MM cells express low levels of CD84. However, these cells secrete the cytokine macrophage migration inhibitory factor (MIF), which induces CD84 expression on cells in their microenvironment. Its activation leads to an elevation of expression of genes regulating differentiation to monocytic/granulocytic-myeloid-derived suppressor cells (M-MDSCs and G-MDSCs, respectively) and upregulation of PD-L1 expression on MDSCs, which together suppress T cell function. Downregulation of CD84 or its blocking reduce MDSC accumulation, resulting in elevated T cell activity and reduced tumor load. Our data suggest that CD84 might serve as a novel therapeutic target in MM.

Glucocorticoid receptor expression in multiple myeloma patients is a predictor of survival.

Multiple myeloma (MM) is a blood neoplasia characterized by abnormal proliferation of plasma cells. Various treatments such as stem cell transplant (SCT), proteasome inhibitors, immune-modulating drugs, monoclonal antibodies and selective inhibitors of nuclear export have been routinely used to treat MM. However, relapse and treatment resistance are common problems in MM patients. Treatments are enhanced by Dexamethasone (Dex), a synthetic steroid that activates the glucocorticoid receptor (GR) which leads to apoptosis. To evaluate the potential impact of GR expression on overall survival, MM patient data from the CoMMpass study of 650 patients were analyzed. Multivariate modeling results show that increased GR expression at diagnosis is associated with a decreased risk of dying relative to those with lower levels of expression.

Strong association between lung cancer and the AXIN2 polymorphism.

Accumulated evidence suggests that alterations due to mutations or genetic polymorphisms in the AXIN2 tumor suppressor gene, a component of the Wnt signaling pathway, contributes to carcinogenesis. The effect of the AXIN2 exon 1 148 C↷T polymorphism was recently investigated in a Japanese population, but has not been investigated in other populations. Additionally, other common polymorphisms of this gene have not been studied. In the present study, 8 polymorphisms of the AXIN2 gene, including exon 1 148 C↷T, were investigated in a Turkish population of 100 lung cancer patients using PCR-RFLP methods. For the exon 1 432 C↷T, exon 5 1365 G↷A, exon 5 1386 C↷T, intron 5 1712+19 G↷T, exon 7 2062 C↷T and intron 7 2141+73 G↷A single nucleotide polymorphisms of AXIN2, no significant association was found between the controls and the lung cancer patients. For exon 1 148 C↷T, a statistically significant association between the controls and lung cancer patients was found. For this region, lung cancer patients with the TT genotype showed a decreased risk [odds ratio (ORTT) 0.33, 95% confidence interval (CI) 0.12-0.89; p=0.032 (adjusted for age, gender and smoking status)] as compared with the controls with the CC genotype. Concerning histological tumor type, it has been found that exon 1 148 C↷T SNP is associated with a significant decreased risk in squamous cell carcinoma patients (ORTT 0.16; 95% CI 0.03-0.79; p=0.014). Male (ORTT 0.19; 95% CI 0.04-0.77; p=0.015) and smoker (ORTT 0.11; 95% CI 0.01-0.71; p=0.019) lung cancer patients with the TT genotype showed a decreased risk for the same region. Our results suggest that the risk of lung cancer in a Turkish population is related to polymorphisms of the AXIN2 gene.