scholarly journals Immunohistochemical Analysis of IL-6, IL-8/CXCR2 Axis, Tyrp-STAT-3, and SOCS-3 in Lymph Nodes from Patients with Chronic Lymphocytic Leukemia: Correlation between Microvascular Characteristics and Prognostic Significance

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Georgia Levidou ◽  
Sotirios Sachanas ◽  
Gerassimos A. Pangalis ◽  
Christina Kalpadakis ◽  
Xanthi Yiakoumis ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Prognostic Significance ◽  
Immunohistochemical Analysis ◽  
Clinicopathological Characteristics ◽  
Lymphocytic Leukemia ◽  
Favorable Effect ◽  
Pathophysiological Role ◽  
Binet Stage ◽  
Insight Into

A number of studies have looked into the pathophysiological role of angiogenesis in CLL, but the results have often been inconsistent. We aimed to gain direct insight into the angiogenic process in lymph nodes involved by CLL, focusing on proangiogenic cytokines and microvessel morphometry. The tissue levels of VEGF, Th-2 cytokines IL-6 and IL-8, IL-8 receptor CXCR2, and tyrosine p-STAT-3/SOCS-3 axis modulating cytokine expression were evaluated immunohistochemically in 62 CLL/SLL cases. Microvascular characteristics were evaluated by image analysis. Results were analyzed with regard to clinicopathological characteristics. Proliferation centers (PCs) were less well vascularised compared to non-PC areas. IL-8 and CXCR2 expression was distinctly uncommon as opposed to IL-6, VEGF and SOCS-3, which were detected in the vast majority of cases. The latter two molecule expressions were more pronounced in the PCs in∼40% of the cases. p-STAT-3 immunoreactivity was recorded in 66.67% of the cases with a predilection for PCs. Microvessel morphometry was unrelated to proangiogenic cytokines, p-STAT-3, SOCS-3, or survival. Microvascular caliber and VEGF expression were higher in Binet stage A, whereasIL-6 expression was higher in stage C. VEGF and p-STAT-3 exerted a favorable effect on progression, which remained significant in multivariate analysis, thereby constituting potential outcome predictors in CLL patients.

scholarly journals Th17 Cells and IL-17 As Novel Immune Targets in Ovarian Cancer Therapy

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Monika Bilska ◽  
Anna Pawłowska ◽  
Ewelina Zakrzewska ◽  
Agata Chudzik ◽  
Dorota Suszczyk ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Th17 Cells ◽  
Prognostic Significance ◽  
Clinicopathological Characteristics ◽  
Lower Percentage ◽  
Benign Tumors ◽  
Control Group ◽  
Intracellular Expression ◽  
Benign Ovarian Tumors

Ovarian cancer (OC) is usually diagnosed at an advanced stage and is related with poor prognosis. Despite numerous studies, the pathogenesis of OC is still unknown. Recent studies indicate the role of the immune system in the development and spread of OC. The identification of factors and mechanisms involved in that process and their modulation is crucial for creating effective antitumor therapy. We investigated the potential role of Th17 cells in OC patients (n = 71) by analyzing the frequencies of Th17 cells in three different environments, i.e., peripheral blood (PB), peritoneal fluid (PF), and tissue (Th17 infiltrating cells), and the concentration of IL-17A in plasma and PF of patients in terms of their clinical and prognostic significance. Th17 cells were analyzed by flow cytometry as a percentage of CD4+ lymphocytes that expressed intracellular expression of IL-17A. The level of IL-17A in plasma and PF were determined by ELISA. Our results showed accumulation of Th17 cells among tumor-infiltrating CD4+ lymphocytes (p<0.001 in relation to PB). Moreover, the percentage of Th17 cells in both PB and PF of OC patients was significantly lower than that in benign tumors group (n = 35). There were no significant differences in the percentage of Th17 cells in PB, PF, and tissue in relation to clinicopathological characteristics of OC patients and survival. The lower percentage of Th17 cells in the PB and PF of OC patients may promote evasion of host immune response by cancer cells. The concentration of IL-17A in plasma of OC patients was higher (p<0.0001) than that in both benign tumors and control group (n = 10). The PF IL-17A level in OC patients was higher (p<0.0001) than that in women with benign ovarian tumors, indicating its synthesis in OC microenvironment. Higher IL-17A level in PF is correlated with longer (median: 36.5 vs. 27 months) survival of OC patients.

scholarly journals CD200 and Chronic Lymphocytic Leukemia: Biological and Clinical Relevance

2020 ◽  
Vol 10 ◽  
Author(s):  
Giovanni D’Arena ◽  
Vincenzo De Feo ◽  
Giuseppe Pietrantuono ◽  
Elisa Seneca ◽  
Giovanna Mansueto ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
T Lymphocytes ◽  
B Cell ◽  
Cell Lymphoma ◽  
Prognostic Significance ◽  
Cell Types ◽  
Lymphocytic Leukemia ◽  
Mantle Cell ◽  
Type Ia

CD200, a transmembrane type Ia glycoprotein belonging to the immunoglobulin protein superfamily, is broadly expressed on a wide variety of cell types, such as B lymphocytes, a subset of T lymphocytes, dendritic cells, endothelial and neuronal cells. It delivers immunosuppressive signals through its receptor CD200R, which is expressed on monocytes/myeloid cells and T lymphocytes. Moreover, interaction of CD200 with CD200R has also been reported to play a role in the regulation of tumor immunity. Overexpression of CD200 has been reported in chronic lymphocytic leukemia (CLL) and hairy cell leukemia but not in mantle cell lymphoma, thus helping to better discriminate between these different B cell malignancies with different prognosis. In this review, we focus on the role of CD200 expression in the differential diagnosis of mature B-cell neoplasms and on the prognostic significance of CD200 expression in CLL, where conflicting results have been published so far. Of interest, increasing evidences indicate that anti-CD200 treatment might be therapeutically beneficial for treating CD200-expressing malignancies, such as CLL.

scholarly journals Dissecting the Prognostic Significance and Functional Role of Progranulin in Chronic Lymphocytic Leukemia

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 822 ◽  
Author(s):  
Lena Schulze-Edinghausen ◽  
Claudia Dürr ◽  
Selcen Öztürk ◽  
Manuela Zucknick ◽  
Axel Benner ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Stromal Cells ◽  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
Cancer Associated Fibroblast ◽  
Survival Gene ◽  
Potential Use

Chronic lymphocytic leukemia (CLL) is known for its strong dependency on the tumor microenvironment. We found progranulin (GRN), a protein that has been linked to inflammation and cancer, to be upregulated in the serum of CLL patients compared to healthy controls, and increased GRN levels to be associated with an increased hazard for disease progression and death. This raised the question of whether GRN is a functional driver of CLL. We observed that recombinant GRN did not directly affect viability, activation, or proliferation of primary CLL cells in vitro. However, GRN secretion was induced in co-cultures of CLL cells with stromal cells that enhanced CLL cell survival. Gene expression profiling and protein analyses revealed that primary mesenchymal stromal cells (MSCs) in co-culture with CLL cells acquire a cancer-associated fibroblast-like phenotype. Despite its upregulation in the co-cultures, GRN treatment of MSCs did not mimic this effect. To test the relevance of GRN for CLL in vivo, we made use of the Eμ-TCL1 CLL mouse model. As we detected strong GRN expression in myeloid cells, we performed adoptive transfer of Eμ-TCL1 leukemia cells to bone marrow chimeric Grn−/− mice that lack GRN in hematopoietic cells. Thereby, we observed that CLL-like disease developed comparable in Grn−/− chimeras and respective control mice. In conclusion, serum GRN is found to be strongly upregulated in CLL, which indicates potential use as a prognostic marker, but there is no evidence that elevated GRN functionally drives the disease.

Abnormal Free Light Chain Ratios in Chronic Lymphocytic Leukemia: A New Prognostic Factor?.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1237-1237 ◽  
Author(s):  
Johannes Matschke ◽  
Lewin Eisele ◽  
Ludger Sellmann ◽  
Ulrich Duehrsen ◽  
Jan Duerig ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Chronic Lymphocytic Leukemia ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Risk Groups ◽  
Typical Feature ◽  
Lymphocytic Leukemia ◽  
Al Amyloidosis ◽  
Abnormal Ratio

Abstract Abstract 1237 Poster Board I-259 Introduction Free light chains (FLC) have prognostic significance in monoclonal gammopathy of undetermined significance, solitary plasmocytoma of bone, smouldering myeloma, multiple myeloma, Waldenstroms macroglobulinaemia and AL amyloidosis. Although monoclonal protein secretion is a typical feature of plasma cell dyscrasias, it can also be detected in other B cell malignancies including chronic lymphocytic leukemia (CLL). Recent data suggest a significant correlation between abnormal ratio of FLC and outcome. Therefore, we investigated FLC in a large cohort of 120 patients in order to assess the role of FLC in CLL. Methods and Results Plasma samples which had been previously cryopreserved and collected at the time before the initiation of therapy or six months after finishing therapy were used. The levels of FLC were assessed using nephelometric immunoassays (The Binding Site) and quantified nephelometrically with the BNII analyser. A normal FLC range (κlγ) was defined as 0.26-1.65. Moreover, in all cases we evaluated the M band on immunofixation (IF). Abnormal FLC ratios were found in 71 patients (59%) whereas the IF was positive in only 32 cases (27%). In 48 cases the FLC ratio was positive while IF was negative and in only 9 cases the IF was positive while the FLC ratio was normal. In total, 23 patients had both a positive IF and an abnormal FLC ratio. Patients with an abnormal FLC ratio for γ had a significantly shorter treatment-free survival (TFS) than patients with an abnormal ratio for κ or with a normal FLC ratio (median TFS: 34 versus 78 versus 109 months, p=0.042). Evaluation of several disease characteristics in association with FLC of the patients' B-CLL cells showed no significant differences for FLC in the different risk groups (ZAP-70 status, CD38 status, cytogenetics and Binet stage) suggesting no correlation of the FLC with these already established adverse prognostic factors. Conclusion FLC can be detected in a substantial fraction of patients with CLL and the FLC technique improves detection of M-proteins. Moreover, an abnormal FLC ratio is associated with worse outcome, particularly those with a low abnormal FLC ratio. Evaluation of the prognostic significance of abnormal FLC in a larger cohort is currently under way. This data will be presented at the meeting. Future studies are warranted to elucidate the role of FLC as biomarkers of disease and as a prognostic factor for response. Disclosures No relevant conflicts of interest to declare.

scholarly journals Pathophysiological role of Atg5 in human ulcerative colitis

2020 ◽  
Vol 18 (4) ◽  
pp. 421-429
Author(s):  
Razieh Ardali ◽  
Nasrin Kazemipour ◽  
Saeed Nazifi ◽  
Kamran Bagheri Lankarani ◽  
Iman Razeghian Jahromi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Samples ◽  
Significant Difference ◽  
Colon Biopsy ◽  
Pathophysiological Role ◽  
Healthy Control ◽  
Inflammatory Bowel ◽  
Insight Into

Background/Aims: Ulcerative colitis (UC), along with Crohn’s disease, is one of the main types of inflammatory bowel disease (IBD). On the other hand, deregulated autophagy is involved in many chronic diseases, including IBD. In this study, we aimed to investigate the role of Atg5 and microRNA-181a (miR-181a) in the pathophysiology of UC. Methods: Colon biopsy, stool, and blood samples of 6 men and 9 women were confirmed for UC. Also, 13 men and 17 women were selected as healthy control (HC). Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to measure the Atg-5 content of the colon biopsies. Besides, the serum and stool levels of Atg5 were measured using ELISA. Moreover, the total RNA of blood cells was extracted and evaluated for the expression of miR-181a.Results: We found 1.2 ng/mL versus 0.46 ng/mL, 0.34 ng/mL versus 0.24 ng/mL, and 0.082 ng/mL versus 0.062 ng/mL of Atg5 in stool, intestinal tissue, and serum of UC and HCs, respectively. There was no significant difference in the expression of miR-181a in the blood samples of UC and HCs. Immunohistochemistry showed high positivity without any significant difference between the 2 groups in the quantitative analysis.Conclusions: The significant difference observed between the stool Atg5 content of the HCs and UC patients may provide new insight into using this protein as a diagnostic biomarker, however, considering the small size of our studied population further studies are needed.

Occurrence of Chromosomal Translocations as Independent Prognostic Factor in Chronic Lymphocytic Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2084-2084
Author(s):  
Christine Mayr ◽  
Cathrine Schulz ◽  
Stephan Stilgenbauer ◽  
Alexander Kröber ◽  
Hartmut Döhner ◽  
...  
Keyword(s):  
Risk Factor ◽  
Prognostic Factors ◽  
High Risk ◽  
Prognostic Factor ◽  
Chronic Lymphocytic Leukemia ◽  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
Chromosomal Translocations ◽  
Study Cohort ◽  
Binet Stage

Abstract Background: The course of chronic lymphocytic leukemia (CLL) is highly variable. Therefore, there is a need for prognostic factors that are readily performed and have a high predictive power. Methods: The occurrence of translocations, a recently identified prognostic factor in CLL (Blood2006;107:742–751), was studied in 148 previously untreated, mostly early-stage patients and compared with respect to treatment-free survival (TFS) to several prognostic factors (Binet stage, mutational status of immunoglobulin genes, CD38, thymidine kinase serum concentration and cytogenetic aberrations detected by interphase FISH). To investigate chromosomal translocations, we applied a new method, CpG oligodeoxynucleotide stimulation that allows efficient preparation of metaphase spreads from CLL cells. Results: The occurrence of translocations classified the majority of patients with poor prognosis. If translocations were investigated in addition to the currently used prognostic factors they identified those patients who were classified to be in a low-risk group based on traditionally used criteria, who had in fact a high risk for progression. Vice versa, patients in the high-risk groups for progression who did not have translocations had a long TFS. There was a substantial overlap of patients who had translocations and additional risk factors. But when we omitted patients who had translocations in addition to a given risk factor, we found that the respective risk factor lost its prognostic significance for the remaining patients. The two factors that retained their prognostic power in these patients were translocations and the Binet stage. This could suggest that the prognostic significance of the currently used factors derives from their frequent co-occurrence with translocations. Finally, multivariate analyses demonstrated that Binet stage (p=0.02) and translocations (p=0.0005) are the factors with the highest impact on TFS in our study cohort. Conclusion: We present a method for efficient preparation of metaphase spreads in CLL cells in order to investigate chromosomal translocations. The occurrence of translocations is an independent prognostic marker in CLL. Finally, translocations occur not as a late event in the course of the disease and may define a new biological subgroup in this disease entity.

scholarly journals Prognostic Significance of Serum Free Light Chains in Chronic Lymphocytic Leukemia

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Katerina Sarris ◽  
Dimitrios Maltezas ◽  
Efstathios Koulieris ◽  
Vassiliki Bartzis ◽  
Tatiana Tzenou ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
Light Chains ◽  
Free Light Chains ◽  
Prognostic Implication ◽  
Time To Treatment ◽  
Serum Free ◽  
Binet Stage ◽  
Serum Free Light Chains

Background. Serum free light chains (sFLC), the most commonly detected paraprotein in CLL, were recently proposed as useful tools for the prognostication of CLL patients.Objective. To investigate the prognostic implication of sFLC and the summated FLC-kappa plus FLC-lambda in a CLL patients’ series.Patients and Methods. We studied 143 CLL patients of which 18 were symptomatic and needed treatment, while 37 became symptomatic during follow-up. Seventy-two percent, 18%, and 10% were in Binet stage A, B and C, respectively. Median patients’ followup was 32 months (range 4–228).Results. Increased involved (restricted) sFLC (iFLC) was found in 42% of patients, while the summated FLC-kappa plus FLC-lambda was above 60 mg/dL in 14%. Increased sFLC values as well as those of summated FLC above 60 were related to shorter time to treatment (P=0.0005andP=0.000003, resp.) and overall survival (P=0.05andP=0.003, resp.). They also correlated withβ2-microglobulin (P=0.009andP=0.03, resp.), serum albumin (P=0.009for summated sFLC), hemoglobin (P<0.001), abnormal LDH (P=0.037andP=0.001, resp.), Binet stage (P<0.05) and with the presence of beta symptoms (P=0.004for summated sFLC).Conclusion. We confirmed the prognostic significance of sFLC in CLL regarding both time to treatment and survival and showed their relationship with other parameters.

scholarly journals Targeting the Immune Microenvironment in Lymphomas of B-Cell Origin: From Biology to Clinical Application

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 915 ◽  
Author(s):  
Mulder ◽  
Wahlin ◽  
Österborg ◽  
Palma
Keyword(s):  
B Cell ◽  
Immune Cells ◽  
Clinical Results ◽  
Lymphocytic Leukemia ◽  
Inflammatory Microenvironment ◽  
Different Types ◽  
Survival And Growth ◽  
Characteristic Features ◽  
Insight Into

In lymphomas of B-cell origin, cancer cells orchestrate an inflammatory microenvironment of immune and stromal cells that sustain the tumor cell survival and growth, known as a tumor microenvironment (TME). The features of the TME differ between the different lymphoma types, ranging from extremely inflammatory, such as in Hodgkin lymphoma, to anergic, leading to immune deficiency and susceptibility to infections, such as in chronic lymphocytic leukemia. Understanding the characteristic features of the TME as well as the interactions between cancer and TME cells has given insight into the pathogenesis of most lymphomas and contributed to identify novel therapeutic targets. Here, we summarize the preclinical data that contributed to clarifying the role of the immune cells in the TME of different types of lymphomas of B-cell origin, and explain how the understanding of the biological background has led to new clinical applications. Moreover, we provide an overview of the clinical results of trials that assessed the safety and efficacy of drugs directly targeting TME immune cells in lymphoma patients.

Autoimmune cytopenia in chronic lymphocytic leukemia: prevalence, clinical associations, and prognostic significance

Blood ◽  
2010 ◽  
Vol 116 (23) ◽  
pp. 4771-4776 ◽  
Author(s):  
Carol Moreno ◽  
Kate Hodgson ◽  
Gerardo Ferrer ◽  
Montse Elena ◽  
Xavier Filella ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Blood Lymphocyte ◽  
Prognostic Significance ◽  
Lymphocytic Leukemia ◽  
Prognostic Variables ◽  
Course Of Disease ◽  
Binet Stage ◽  
Clinical Associations ◽  
Autoimmune Cytopenia ◽  
Massive Bone

AbstractWe analyzed prevalence, characteristics, clinical correlates, and prognostic significance of autoimmune cytopenia in patients with chronic lymphocytic leukemia. Seventy of 960 unselected patients (7%) had autoimmune cytopenia, of whom 19 were detected at diagnosis, 3 before diagnosis, and 48 during the course of the disease. Forty-nine patients had autoimmune hemolytic anemia, 20 had immune thrombocytopenic purpura, and 1 had both conditions. A clear association was observed between autoimmune cytopenia and poor prognostic variables (ie, high blood lymphocyte count, rapid blood lymphocyte doubling time, increased serum β-2 microglobulin level, and high expression of ζ-associated protein 70 and CD38). Nevertheless, the outcome of patients with autoimmune cytopenia as a whole was not significantly different from that of patients without this complication. Furthermore, no differences were observed according to time at which cytopenia was detected (ie, at diagnosis, during course of disease). Importantly, patients with advanced (Binet stage C) disease because of an autoimmune mechanism had a significantly better survival than patients in advanced stage related to a massive bone marrow infiltration (median survivals: 7.4 years vs 3.7 years; P = .02). These results emphasize the importance of determining the origin of cytopenia in patients with chronic lymphocytic leukemia for both treatment and prognostic purposes.

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