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In the last few years, it has been suggested that the involvement of human leukocyte antigen-G (HLA-G) in several tumoral processes and its likely participation as a factor of immune tolerance in malignant cells. Recently, positive HLA-G surface expression has been associated with a poor prognosis in a small group of patients with B-cell chronic lymphocytic leukemia (B-CLL), a lymphoproliferative disorder characterized by a heterogeneous clinical course. In the present work, 169 patients suffering from B-CLL were analyzed for the expression of HLA-G by flow cytometry in order to verify its prognostic value in a larger cohort. We observed a low expression of this molecule on leukemic B cells and no significant relation to clinical data or progression-free survival time, indicating that this molecule is not as good immunologic prognostic marker for B-CLL as suggested. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine whether several allelic variants in the polymorphic interleukin (IL)-10 promoter region were related with an increased risk of developing systemic lupus erythematosus (SLE) in Spanish patients from Canary Islands. Microsatellites (MS) at positions –4000 and –1200 (IL10R and IL10G, respectively) and single nucleotide polymorphisms (SNPs) (MS) at positions –1082G/A, –819C/T and –592C/A of the IL-10 promoter were analysed in patients with SLE and healthy controls from Canary Islands (Spain). We found that SNPs but not MS were associated with SLE. The GCC haplotype frequency was significantly higher in SLE patients (0.43) than in healthy donors (0.33) [ P = 0.02; OR = 1.50 (95% CI = 1.06–2.14)], whereas the ACC haplotype was less represented in patients (0.28 vs. 0.37) [ P = 0.02; OR = 0.64 (95% CI = 0.44–0.92)]. To assess the functional role of genotypes, serum IL-10 levels from patients and controls were quantified by ELISA. Also, the lipopolysaccharide-induced IL-10 secretion by monocytes from healthy controls was evaluated in vitro. Serum IL-10 levels were higher in patients [median (interquartile range) = 2.8 pg/mL (1.8–4.2)] than in controls [0.9 pg/mL (0–3.5)] ( P = 0.02), but no association was observed between serum IL-10 levels or lipopolysaccharide-induced IL-10 secretion and the IL-10 promoter haplotypes. These data suggest that the IL-10 promoter haplotype that produces higher levels of cytokine is associated with SLE in patients from Canary Islands. [ABSTRACT FROM AUTHOR]

Despite strong preclinical data, the therapeutic benefit of the RANKL inhibitor, denosumab, in breast cancer patients, beyond the bone, is unclear. Aiming to select patients who may benefit from denosumab, we hereby analyzed RANK and RANKL protein expression in more than 2,000 breast tumors (777 estrogen receptor-negative, ER - ) from four independent cohorts. RANK protein expression was more frequent in ER - tumors, where it associated with poor outcome and poor response to chemotherapy. In ER - breast cancer patient-derived orthoxenografts (PDXs), RANKL inhibition reduced tumor cell proliferation and stemness, regulated tumor immunity and metabolism, and improved response to chemotherapy. Intriguingly, tumor RANK protein expression associated with poor prognosis in postmenopausal breast cancer patients, activation of NFKB signaling, and modulation of immune and metabolic pathways, suggesting that RANK signaling increases after menopause. Our results demonstrate that RANK protein expression is an independent biomarker of poor prognosis in postmenopausal and ER - breast cancer patients and support the therapeutic benefit of RANK pathway inhibitors, such as denosumab, in breast cancer patients with RANK + ER - tumors after menopause., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)