Preoperative neutrophil-lymphocyte and lymphocyte-monocyte ratios reflect immune cell population rearrangement in resectable pancreatic cancer

BACKGROUND: Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) may serve as a simple index of the immune function. The aim of this study was to investigate the prognostic significance of NLR, PLR, and LMR in patients with resectable pancreatic ductal adenocarcinoma (PDAC) and to verify whether such biomarkers are associated with changes in populations of lymphoid cells. METHODS: The prognostic implications of blood count parameters were evaluated in a retrospective cohort of 442 subjects undergoing pancreatic resections for PDAC. Subpopulations of lymphocytes and monocytes in peripheral blood were identified by FACS in a prospective cohort of 54 patients. RESULTS: In the univariate analysis, NLR < 5 and LMR ≥ 3 were associated with significantly longer median survival of 25.7 vs 12.6 months and 29.2 vs 13.1 months, respectively. PLR did not influence survival. The Cox proportional hazards model showed that high NLR (HR 1.66, 95 % CI 1.12 to 2.46, P = 0.012) and low LMR (HR 1.65, 95 % CI 1.06 to 2.58, P = 0.026) were independent predictors of poor prognosis. NLR ≥ 5 and LMR < 3 correlated with an approximately twofold decrease in counts of helper and cytotoxic T cells, B cells, and NK cells. High NLR was also accompanied with increased neutrophil counts, while low LMR showed increased numbers of monocytes, mostly classical. CONCLUSIONS: NLR and LMR may carry important prognostic information for patients with resected PDAC. The unfavorable prognosis likely correlates with reduced numbers of immune cells effective against the tumor and increased populations of cells involved in immune suppression

Analysis of PD-1 expression in the monocyte subsets from non-septic and septic preterm neonates

Programmed death-1 (PD-1) receptor system represents a part of recently reported immunoregulatory pathway. PD-1 is an immune checkpoint molecule, which plays an important role in downregulating the immune system proinflammatory activity. Until recently, PD-1 expression was not established on immune cells of the preterm infants. The study objectives were to confirm expression of the PD-1 receptors on the monocytes isolated from very low birth weight newborns (VLBW), and to analyze their expression during the first week of life and late-onset sepsis. Peripheral blood mononuclear cells were isolated from 76 VLBW patients without early-onset sepsis on their 5th day of life (DOL). PD-1 expression was determined on the monocyte subsets (classical, intermediate, non-classical) by flow cytometry. In case of late-onset sepsis (LOS), the same analysis was performed. Our results demonstrated that on the 5th DOL, PD-1 receptors were present in all the monocyte subsets. Children, whose mothers had received antenatal steroids, presented higher absolute numbers of non-classical monocytes with PD-1 expression. Infants born extremely preterm who later developed LOS, initially showed a lower percentage of PD-1 receptor-positive intermediate monocytes in comparison to neonates born very preterm. During LOS, we observed a rise in the percentage of classical monocytes with PD-1 expression. In case of septic shock or fatal outcome, there was a higher percentage and absolute count of intermediate monocytes with PD-1 expression in comparison to children without these complications. In conclusion, monocytes from VLBW children express PD-1 receptors. Antenatal steroid administration seems to induce PD-1 receptor expression in the non-classical monocytes. PD-1 might play a role in immunosuppressive phase of sepsis in the prematurely born children with septic shock and fatal outcome

The absolute number of circulating nonclassical (CD14+CD16++CD14^{+}CD16^{++}) monocytes negatively correlates with DAS28 and swollen joint count in patients with peripheral spondyloarthritis

A different clinical course and pattern of skeletal involvement in peripheral and axial spondyloarthritis (SpA) suggests a distinct pathophysiology of these 2 phenotypic manifestations of SpA. Monocytes, as part of the innate immune system, seem to play an important role in the pathogenesis of SpA, but the exact inflammatory pathways remain to be elucidated. Regulatory T lymphocytes ($T_{reg}$) and Th17 lymphocytes are also known to influence proinflammatory and anti‑inflammatory reactions. The aim of our study was to compare the absolute numbers of monocyte subpopulations, $T_{reg}$, and Th17 lymphocytes with clinical measures of disease activity in patients with peripheral and axial SpA. We enrolled 21 patients with peripheral SpA and 27 patients with axial SpA diagnosed according to the Assessment of SpondyloArthritis International Society classification criteria, as well as 23 healthy controls. Patients were under 45 years, naïve to synthetic and biological disease‑modifying antirheumatic drugs and without the administration of systemic glucocorticoids. The absolute numbers of classical, intermediate, nonclassical monocytes, $T_{reg}$, and Th17 in peripheral blood were analyzed. Disease activity was assessed using the Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Disease Activity Score 28 (DAS28). In patients with SpA, the number of circulating nonclassical monocytes was decreased in comparison with controls. Only in the peripheral SpA group, a significant negative correlation was found between the concentration of nonclassical monocytes and DAS28 and the number of swollen joints. The 3 groups did not differ in terms of the concentrations of classical or intermediate monocytes and $T_{reg}$ or Th17 lymphocytes. Nonclassical monocytes may play a role in induction and perpetuation of peripheral joint inflammation, at least in peripheral SpA, as cells infiltrating the synovium

Monocyte subpopulations display disease-specific miRNA signatures depending on the subform of Spondyloarthropathy

Spondyloarthropathies (SpA) are a family of rheumatic disorders that could be divided into axial (axSpA) and peripheral (perSpA) sub-forms depending on the disease clinical presentation. The chronic inflammation is believed to be driven by innate immune cells such as monocytes, rather than self-reactive cells of adaptive immune system. The aim of the study was to investigate the micro-RNA (miRNA) profiles in monocyte subpopulations (classical, intermediate and non-classical subpopulations) acquired from SpA patients or healthy individuals in search for prospective disease specific and/or disease subtype differentiating miRNA markers. Several SpA-specific and axSpA/perSpA differentiating miRNAs have been identified that appear to be characteristic for specific monocyte subpopulation. For classical monocytes, upregulation of miR-567 and miR-943 was found to be SpA-specific, whereas downregulation of miR-1262 could serve as axSpA-differentiating, and the expression pattern of miR-23a, miR-34c, mi-591 and miR-630 as perSpA-differentiating markers. For intermediate monocytes, expression levels of miR-103, miR-125b, miR-140, miR-374, miR-376c and miR-1249 could be used to distinguish SpA patients from healthy donors, whereas the expression pattern of miR-155 was identified as characteristic for perSpA. For non-classical monocytes, differential expression of miR-195 was recognized as general SpA indicator, while upregulation of miR-454 and miR-487b could serve as axSpA-differentiating, and miR-1291 as perSpA-differentiating markers. Our data indicate for the first time that in different SpA subtypes, monocyte subpopulations bear disease-specific miRNA signatures that could be relevant for SpA diagnosis/differentiation process and may help to understand SpA etiopathology in the context of already known functions of monocyte subpopulations