scholarly journals Immunohistochemical Expression of Vitamin D Receptor and Forkhead Box P3 in Classic Hodgkin Lymphoma: Correlation with Clinical and Pathologic Findings

2020 ◽  
Author(s):  
Gaurav Gupta ◽  
Tanupriya Agrawal ◽  
Monika Pilichowska
Keyword(s):  
Vitamin D ◽  
T Cells ◽  
Hodgkin Lymphoma ◽  
Vitamin D Receptor ◽  
Clinical Stage ◽  
Foxp3 Expression ◽  
Immunohistochemical Expression ◽  
Forkhead Box P3 ◽  
Forkhead Box ◽  
Classic Hodgkin Lymphoma

Abstract Background Expression of forkhead box P3 (FOXP3), a key regulator of T-cell function, in the tumor immune microenvironment is related to survival in classic Hodgkin lymphoma (CHL). Vitamin D receptor (VDR), a transcription factor , agonists have been shown to induce FOXP3 expression in T-cells and enhance recruitment of these cells to the inflammatory sites. VDR expression is CHL has beenis described. However, there is no data on expression of VDR in context of quantity of FOXP3 positiveexpressing cells in CHL. Methods We examined and correlated immunohistochemical expression of VDR and FOXP3 along with clinical and pathology findings in 29 cases of CHL. Results VDR was expressed in Hodgkin Reed-Sternberg (HRS) cells and background lymphocytes and FOXP3 was expressed in background lymphocytes. 82% of CHL cases, regardless of the subtype, expressed VDR and in majority of the cases, VDR expression was directly proportional to the quantity of FOXP3 expressing lymphocytes in the tumor microenvironment. In cases with higher clinical stage (III/IV), only 28.5% of cases diffusely expressed VDR and FOXP3 compared to 71.4% showing focal positivity. Whereas in cases with lower clinical stages (I/II), the expression pattern of VDR and FOXP3 was almost similar (41.6% diffuse versus 33.3% focal). Interestingly, focal VDR and FOXP3 expression pattern was significantly higher among males. Mixed cellularity cases showed predilection for focal VDR and FOXP3 expression (80% cases); whereas nodular sclerosis subtype had focal and diffuse VDR and FOXP3 expression patterns in similar proportion. Cases with diffuse VDR and FOXP3 expression were less likely to have bone marrow involvement. Epstein Barr virus- encoded small RNA (EBER) positive cases were predominantly focally positive (80%) for VDR and FOXP3. Conclusions In summary, quantity of FOXP3 positive T-cells in CHL microenvironment seems to correlate with VDR expression. Clinical stage show a trend of inverse correlation with expression of VDR and quantity of FOXP3 positive T-cells. These findings suggest that VDR could be a possible prognostic and therapeutic target in CHL.

scholarly journals Immunohistochemical Expression of Vitamin D Receptor and Forkhead Box P3 in Classic Hodgkin Lymphoma: Correlation with Clinical and Pathologic Findings

2020 ◽  
Author(s):  
Gaurav Gupta ◽  
Tanupriya Agrawal ◽  
Monika Pilichowska
Keyword(s):  
Vitamin D ◽  
T Cells ◽  
Hodgkin Lymphoma ◽  
Vitamin D Receptor ◽  
Clinical Stage ◽  
Foxp3 Expression ◽  
Immunohistochemical Expression ◽  
Forkhead Box P3 ◽  
Forkhead Box ◽  
Classic Hodgkin Lymphoma

Abstract Background Expression of forkhead box P3 (FOXP3), a key regulator of T-cell function, in the tumor immune microenvironment is related to survival in classic Hodgkin lymphoma (CHL). Vitamin D receptor (VDR), a transcription factor, agonists have been shown to induce FOXP3 expression in T-cells and enhance recruitment of these cells to the inflammatory sites. VDR expression is CHL has been described. However, there is no data on expression of VDR in context of quantity of FOXP3 positive cells in CHL. Methods We examined and correlated immunohistochemical expression of VDR and FOXP3 along with clinical and pathology findings in 29 cases of CHL. Results VDR was expressed in Hodgkin Reed-Sternberg (HRS) cells and background lymphocytes and FOXP3 was expressed in background lymphocytes. 82% of CHL cases, regardless of the subtype, expressed VDR and in majority of the cases, VDR expression was directly proportional to the quantity of FOXP3 expressing lymphocytes in the tumor microenvironment. In cases with higher clinical stage (III/IV), only 28.5% of cases diffusely expressed VDR and FOXP3 compared to 71.4% showing focal positivity. Whereas in cases with lower clinical stages (I/II), the expression pattern of VDR and FOXP3 was almost similar (41.6% diffuse versus 33.3% focal). Interestingly, focal VDR and FOXP3 expression pattern was significantly higher among males. Mixed cellularity cases showed predilection for focal VDR and FOXP3 expression (80% cases); whereas nodular sclerosis subtype had focal and diffuse VDR and FOXP3 expression patterns in similar proportion. Cases with diffuse VDR and FOXP3 expression were less likely to have bone marrow involvement. Epstein Barr virus- encoded small RNA (EBER) positive cases were predominantly focally positive (80%) for VDR and FOXP3. Conclusions In summary, quantity of FOXP3 positive T-cells in CHL microenvironment seems to correlate with VDR expression. Clinical stage show a trend of inverse correlation with expression of VDR and quantity of FOXP3 positive T-cells. These findings suggest that VDR could be a possible prognostic and therapeutic target in CHL.

scholarly journals Immunohistochemical Expression of Vitamin D Receptor and Forkhead Box P3 in Classic Hodgkin Lymphoma: Correlation with Clinical and Pathologic Findings

2019 ◽  
Author(s):  
Gaurav Gupta ◽  
Tanupriya Agrawal ◽  
Monika Pilichowska
Keyword(s):  
Vitamin D ◽  
T Cells ◽  
Hodgkin Lymphoma ◽  
Vitamin D Receptor ◽  
Clinical Stage ◽  
Foxp3 Expression ◽  
Immunohistochemical Expression ◽  
Forkhead Box P3 ◽  
Forkhead Box ◽  
Classic Hodgkin Lymphoma

Abstract Expression of forkhead box P3 (FOXP3), a key regulator of T-cell function, in the tumor immune microenvironment is related to survival in classic Hodgkin lymphoma (CHL). Vitamin D receptor (VDR), a transcription factor, agonists have been shown to induce FOXP3 expression in T-cells and enhance recruitment of these cells to the inflammatory sites. VDR expression is CHL is described. However, there is no data on expression of VDR in context of quantity of FOXP3 expressing cells in CHL. We examined and correlated immunohistochemical expression of VDR and FOXP3 with clinical and pathology findings in 29 cases of CHL. VDR was expressed in Hodgkin Reed-Sternberg (HRS) cells and background lymphocytes and FOXP3 was expressed in background lymphocytes. 82% of CHL cases, regardless of the subtype, expressed VDR and in majority of the cases, VDR expression was directly proportional to the quantity of FOXP3 expressing lymphocytes in the tumor microenvironment. In cases with higher clinical stage (III/IV), only 28.5% of cases diffusely expressed VDR and FOXP3 compared to 71.4% showing focal positivity. Whereas in cases with lower clinical stages (I/II), the expression pattern of VDR and FOXP3 was almost similar (41.6% diffuse versus 33.3% focal). Interestingly, focal VDR and FOXP3 expression pattern was significantly higher among males. Mixed cellularity cases showed predilection for focal VDR and FOXP3 expression (80% cases); whereas nodular sclerosis subtype had focal and diffuse VDR and FOXP3 expression patterns in similar proportion. Cases with diffuse VDR and FOXP3 expression were less likely to have bone marrow involvement. Epstein Barr virus- encoded small RNA (EBER) positive cases were predominantly focally positive (80%) for VDR and FOXP3. In summary, quantity of FOXP3 positive T-cells in CHL microenvironment seems to correlate with VDR expression. Clinical stage show a trend of inverse correlation with expression of VDR and quantity of FOXP3 positive T-cells. These findings suggest that VDR could be a possible prognostic and therapeutic target in CHL.

scholarly journals CD70+ non-Hodgkin lymphoma B cells induce Foxp3 expression and regulatory function in intratumoral CD4+CD25− T cells

Blood ◽  
2007 ◽  
Vol 110 (7) ◽  
pp. 2537-2544 ◽  
Author(s):  
Zhi-Zhang Yang ◽  
Anne J. Novak ◽  
Steven C. Ziesmer ◽  
Thomas E. Witzig ◽  
Stephen M. Ansell
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Foxp3 Expression ◽  
Regulatory Function ◽  
Forkhead Box P3 ◽  
Non Hodgkin Lymphoma ◽  
Forkhead Box

Foxp3 expression was initially thought to be restricted to the CD4+CD25+ regulatory T-cell population. However, recent studies suggest that forkhead box P3 (Foxp3) is expressed in CD4+CD25− T cells in aged mice. In the present study in B-cell non-Hodgkin lymphoma (NHL), we found that a subset of intratumoral but not peripheral blood CD4+CD25− T cells, comprising about 15% of intratumoral CD4+ T cells, express Foxp3 and are capable of suppressing the proliferation of autologous infiltrating CD8+ T cells. In vitro activation with OKT3/anti-CD28 antibody (Ab) or dendritic cells (DCs) induced Foxp3 expression in a subset of these CD4+CD25−Foxp3− T cells. We found that the presence of lymphoma B cells during activation augmented activation-induced Foxp3 expression in CD4+CD25− T cells. We also found that CD70+ lymphoma B cells significantly contributed to the activation-induced Foxp3 expression in intratumoral CD4+CD25− T cells. Furthermore, the blockade of CD27-CD70 interaction by anti-CD70 Ab abrogated lymphoma B-cell–mediated induction of Foxp3 expression in intratumoral CD4+CD25− T cells. Taken together, these studies reveal a novel role for NHL B cells in the development of intratumoral regulatory T cells.

scholarly journals Vitamin D receptor expression in SLE peripheral blood CD4+T cells is associated with disease activity and cell apoptosis

2021 ◽  
Author(s):  
Ying Zhang ◽  
Lingying Niu ◽  
Fan Wang ◽  
Xiaojun Tang ◽  
Chun Wang ◽  
...  
Keyword(s):  
Vitamin D ◽  
T Cells ◽  
Disease Activity ◽  
Vitamin D Receptor ◽  
Cell Apoptosis ◽  
Cd4 T Cells ◽  
Activity Index ◽  
Receptor Expression ◽  
Th2 Cells ◽  
Tfh Cells

ABSTRACT Objectives Systemic lupus erythematosus (SLE) is characterised by accumulated cell apoptosis. Vitamin D receptor (VDR) has immunomodulatory effect and potent anti-apoptosis activities. The aim of this study was to examine the correlation between CD4+T cells VDR expression, cell apoptosis, and disease activity in patients with SLE. Methods Forty-five SLE patients were recruited and 50 healthy individuals served as controls. The expression of VDR in CD4+T cells and their subsets were determined by flow cytometry. The correlations between VDR expression and cell apoptosis or disease parameters in SLE patients were analysed. Results VDR expression in CD4+T cells and their subsets were upregulated in SLE patients, especially in help T (Th)1, regulatory T (Treg), and follicular helper T (Tfh) cells. Frequency of VDR-positive CD4+T cells was positively associated with SLE disease activity index (SLEDAI)-2K values and inversely correlated with serum C3 concentration. The frequency of VDR-positive CD4+T cells, Th1 cells, Th2 cells, Th17 cells, Treg cells, and Tfh cells was positively correlated with cells apoptosis. Conclusion VDR expression in CD4+T cells and their subsets were increased in SLE. VDR expression was positively associated with disease activity and cell apoptosis in SLE patients.

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