Prognostic value of circulating T-lymphocyte subsets in advanced pancreatic cancer patients treated with mFOLFIRINOX or gemcitabine.

Advanced pancreatic ductal adenocarcinoma (PDAC) is commonly treated with a chemotherapy combination of mFOLFIRINOX or gemcitabine. However, predictive and prognostic factors for choosing a more appropriate treatment strategy are still lacking. This study aimed to evaluate how chemotherapy changes immune system parameters and whether these changes influence survival outcomes. We sought to identify an easily accessible marker to help choose the appropriate treatment. Patients with PDAC who were suitable for systemic chemotherapy were eligible for the study. Peripheral blood samples were obtained at baseline and after two months of treatment. Lymphocyte subsets were measured using flow cytometry. Correlation with clinical features and survival analyses were performed. In total, 124 patients were enrolled in this study. Seventy patients were treated with mFOLFIRINOX and 50 with gemcitabine monotherapy. Four patients could not be treated because of rapid deterioration. During overall survival analysis (OS), significant factors included age, Eastern Cooperative Oncology Group (ECOG) performance status, differentiation grade G3, carcinoma antigen (CA) 19-9 more than 100 kU/L, absolute white blood cell count, CD3 + CD8+, and CD8 + CD57-T lymphocytes. Natural killer CD3-CD56 + CD16 + and CD3-CD56 + CD16- and T regulatory CD4 + FOXP3 + and CD3 + CD56 + cells differed during treatment, but these differences did not influence the survival results. At baseline, CD8 + CD57- T lymphocyte count demonstrated a clear independent impact on progression-free survival and OS. Gemcitabine showed better survival in patients with extremely low baseline CD8 + CD57- levels. Therefore, circulating CD3 + CD8 + and CD8 + CD57- cells measured before treatment in PDAC may be considered prognostic and predictive biomarkers.

The Effects of Treatment on Peripheral Blood Immune Cell Profile in Pancreatic Ductal Adenocarcinoma (PDAC).

BACKGROUND/AIM: This study evaluated whether circulating lymphocytes, assessed by flow cytometry, is a prognostic biomarker in pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: We studied T cell subsets in blood samples from a cohort of 41 patients diagnosed with PDAC. Patients underwent surgery of the primary site and adjuvant chemotherapy or were treated with 1st line chemotherapy (mFOLFIRINOX regimen or gemcitabine alone). The changes in T cell subpopulations during treatment were evaluated at the initial diagnosis before surgery, and after 2 and 4 months. Friedman test was used for statistical analysis. RESULTS: A decline in CD19+ B lymphocytes, natural killer (NK) cells CD3-CD56+CD16+, and T regulatory cells CD4+FOXP3+ during treatment was observed. NKT-like cells CD3+CD56+ and cytotoxic T cells CD3+CD8+ tended to increase after two months and decrease after that. CONCLUSION: Statistically significant changes in lymphocyte counts in peripheral blood were detected in patients with PDAC during treatment.

Changes in circulating endothelial microvesicles in men after myocardial infarction.

PURPOSE: The objective of the study was to determine the differences in the numbers of endothelial microvesicles (EMV) after myocardial infarction (MI) and their association with oxidative stress. MATERIALS AND METHODS: We included 15 post MI patients and 28 healthy controls. Samples were analysed by flow cytometry. We examined four EMV populations: 1) CD144+, CD42a-, CD61-, 2) CD144+, CD42a+, CD61-, 3) CD105+, CD42a-, CD61-and 4) CD31+, CD42a-, CD61-and determined a percentage of CD62e + EMV. Malondialdehyde concentration was determined by ultra-high performance liquid chromatography. RESULTS: The median of EMV counts differed between controls and patients in: CD105+ (10.91 microvesicles/µl vs. 33.68 microvesicles/µl, P = 0.006), CD144+, CD42a+ (312.87 microvesicles/µl vs. 73.29 microvesicles/µl, P < 0.001) and CD31+ (2 microvesicles/µl vs. 1.38 microvesicles/µl, P = 0.021). The median of percentage of CD62e expression differed between controls and patients in: CD105+ (1.35% vs. 14.8%, P < 0.001), CD144+, CD42a+ (56.45% vs. 98.99%, P < 0.001) and CD144+, CD42a- (173.03% vs. 215.56%) EMV. In patients, EMV counts correlated with low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) concentrations: CD105+: R = -0.69, P = 0.004 (LDL-C), R = -0.64, P = 0.01 (TC); CD144+, CD42a-: R = -0.68, P = 0.005 (LDL-C), R = -0.63, P = 0.011 (TC); CD144+: R = -0.54, P = 0.038 (HDL-C) and CD144+, CD42a-, CD62e+: R = 0.78, P = 0.001 (HDL-C). In controls, HDL-C concentration correlated with CD105+ (R = -0.395, P = 0.038) and CD105+, CD62e+ (R = -0.716, P < 0.001) counts. Malondialdehyde concentration correlated with CD144+, CD42a- (P = 0.01, R = 0.48) and CD105+, CD62e+ (P = 0.012, R = 0.47) counts. CONCLUSIONS: Changes in EMV levels after the MI period were observed. Counts of EMV and their CD62e expression correlated with dyslipidaemia and oxidative stress.

Association of Hair Cortisol Concentration with Prevalence of Major Cardiovascular Risk Factors and Allostatic Load.

BACKGROUND The high prevalence of cardiovascular diseases cannot be explained completely by conventional risk factors such as older age, smoking, diabetes mellitus, hypertension, obesity, and dyslipidemia. Results of recent studies indicate that chronic stress may be an independent risk factor for cardiovascular morbidity and mortality. Thus, the aim of our study was to investigate the associations between the hair cortisol concentration (HCC), which is considered as a potential biomarker of long-term psychosocial stress, and traditional cardiovascular risk factors, including smoking, dyslipidemia, hypertension, and obesity. MATERIAL AND METHODS Fasting blood samples and anthropometric and lifestyle data were collected from 163 apparently healthy men. HCC was determined using high-performance liquid chromatography. Allostatic load (AL) index, defined as an integrated score of multiple interacting systems involved in the adaptation to adverse physical or psychosocial situations, was also calculated. RESULTS We found that many prevalent cardiovascular risk factors, including hypertension, smoking, higher than recommended waist circumference (WC), and low-density lipoprotein cholesterol (LDL-C) median values, are associated with higher HCC. Hair cortisol level was also positively associated with the manifestation of individual cardiovascular risk factors such as higher-than-recommended total cholesterol, LDL-C, non-high-density lipoprotein cholesterol, body mass index, and WC median values. Moreover, a significant positive relationship between HCC and AL index was observed. CONCLUSIONS The results of this study suggest that increased prevalence of traditional cardiovascular risk factors is associated with higher HCC. Also, both HCC and AL index might be appropriate markers for the evaluation of chronic stress level.

Circulating plasma cells predict the outcome of relapsed or refractory multiple myeloma.

Pretreatment detection of peripheral blood malignant circulating plasma cells (CPCs) has been shown to be of negative prognostic value in multiple myeloma (MM). We hypothesized that the assessment of CPC kinetics in response to one therapy cycle using six-color flow cytometry could be helpful in the early detection of MM refractoriness to treatment. Forty-two patients with refractory or relapsed (RR) MM were enrolled. Median time to tumor progression (TTP) of 51 days and median overall survival (OS) of 308 days was shortest in patients whose CPCs with aberrant phentoype (aCPCs) did not decrease after one therapy cycle compared to patients with decreasing (median TTP 258 days and OS 856 days) or undetectable (median TTP 581 days and OS 1006 days) aCPCs (p < 0.001 and p = 0.007 for TTP and OS, respectively). Non-reduction of aCPCs in patients with RR MM after the first cycle of therapy may be useful in early identification of patients resistant to a given therapy.

Six color flow cytometry detects plasma cells expressing aberrant immunophenotype in bone marrow of healthy donors.

BACKGROUND: Both normal and malignant plasma cell (PC) populations can be identified using modern flow cytometry (FC) technique in multiple myeloma (MM) patients. Expression of CD19 and CD56 markers is heterogenous on bone marrow PCs of healthy individuals. Little is known about immunophenotypically aberrant (CD19-/CD56+) PCs subpopulation of healthy people. METHODS: Using six color FC, we analyzed PCs in BM samples of 11 healthy donors (HD) and compared their immunophenotypic properties with clonal PC populations from MM patients. RESULTS: Both immunophenotypically normal (CD19+/CD56-) and aberrant (CD19-/CD56+) PC populations could be detected in 10 of 11 HDs' BM samples and constituted the median of 60.3% (37.3-72.3) and 9.6% (0-35.7) of BM PCs, respectively. CD19, CD56, CD38, CD45, and CD20 marker expression characteristics were of little value discriminating clonal PCs of MM patients from immunophenotypically aberrant PCs of healthy donors. CONCLUSIONS: Our findings suggest that aberrant immunophenotype is common in BM PCs of healthy people. Improvements in FC methodology to separate normal and malignant PCs remain an open area for future investigations.