scholarly journals Cluster of Differentiation 274 Antigen Immunohistochemical Expression in Tumor and Peri-tumor Cells of Hodgkin and Non-Hodgkin Lymphoma and Clinicopathological Relation (Single-center Study)

2021 ◽  
Vol 9 (A) ◽  
pp. 1011-1018
Author(s):  
Walaa Ghanam ◽  
Shaimaa M. M. Bebars
Keyword(s):  
Hodgkin Lymphoma ◽  
Tumor Cells ◽  
Lymph Node Excision ◽  
Excision Biopsy ◽  
Immunohistochemical Expression ◽  
High Power Field ◽  
Non Hodgkin Lymphoma ◽  
Classic Hodgkin Lymphoma ◽  
Significant Expression ◽  
Cluster Of Differentiation

BACKGROUND: Cluster of differentiation 274 (CD274) antigen has been investigated in tumors to evaluate its regulation and effect as a predictive of targeted therapy. Its expression and effect in lymphoma have raised interest recently. However, results were mixed and showed wide variations. AIM: This study aims to explore and compare CD274 antigen immunohistochemical expression in tumor and peri-tumor cells of classic Hodgkin lymphoma (HL) and diffuse large B cells non-HL (NHL) and its relation with clinicopathological criteria. METHODS: This work was carried out on 78 cases of lymph node excision biopsy (48 HL and 30 NHL). Prepared sections were applied for immunohistochemistry using CD274 monoclonal rabbit anti-human (programmed cell death protein 1 [PD-L1] ZR3-ASR, a Sigma Aldrich company). Assessment of CD274 antigen in tumor cells was considered positive if detected in >10% (membranous staining with cytoplasmic accentuation). Peri-tumor cells were scored as: 0, no positive cells/high-power field (HPF); 1, <10 positive cells/HPF; 2, 10–30 positive cells/HPF; 3, >30 positive cells/HPF. RESULTS: CD274 antigen was expressed in 53.8% of total lymphoma cases with significantly more expression of CD274 antigen in HL than NHL (66.7% vs. 33.3%). Classic HL showed significantly higher expression of CD274 antigen in tumor and peri-tumor cells and significant association with elevated erythrocyte sedimentation rate and lactate dehydrogenase and male gender. INTERPRETATION AND CONCLUSION: There is a more frequent and significant expression of CD274 antigen in classic HL than NHL cases in tumor and peri-tumor cells and a significant association with bad prognostic criteria in classic HL. High expression of CD274 antigen in classic HL proposes its potential use as a marker, especially for prognostic indication.

Proangiogenic cytokines produced by non-Hodgkin lymphoma tumor cells induce angiogenesis in infiltrated bone marrow samples

2009 ◽  
Vol 50 (8) ◽  
pp. 1381-1383 ◽  
Author(s):  
Leina Yukari Etto ◽  
Maria Regina Regis Silva ◽  
Maria Aparecida Dalboni ◽  
Antonio Correa Alves ◽  
Gisele W. B. Colleoni
Keyword(s):  
Bone Marrow ◽  
Hodgkin Lymphoma ◽  
Tumor Cells ◽  
Non Hodgkin Lymphoma

scholarly journals Formation of the Immunosuppressive Microenvironment of Classic Hodgkin Lymphoma and Therapeutic Approaches to Counter It

2019 ◽  
Vol 20 (10) ◽  
pp. 2416 ◽  
Author(s):  
Donatella Aldinucci ◽  
Cinzia Borghese ◽  
Naike Casagrande
Keyword(s):  
T Cell ◽  
Tumor Microenvironment ◽  
Hodgkin Lymphoma ◽  
Tumor Cells ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
T Cell Exhaustion ◽  
Normal Cells ◽  
Cell Exhaustion ◽  
Classic Hodgkin Lymphoma

Classic Hodgkin lymphoma (cHL) is characterized by a few tumor cells surrounded by a protective, immunosuppressive tumor microenvironment composed of normal cells that are an active part of the disease. Hodgkin and Reed–Sternberg (HRS) cells evade the immune system through a variety of different mechanisms. They evade antitumor effector T cells and natural killer cells and promote T cell exhaustion. Using cytokines and extracellular vesicles, they recruit normal cells, induce their proliferation and “educate” (i.e. reprogram) them to become immunosuppressive and protumorigenic. Therefore, alternative treatment strategies are being developed to target not only tumor cells but also the tumor microenvironment. Here we summarize current knowledge on the ability of HRS cells to build their microenvironment and to educate normal cells to become immunosuppressive. We also describe therapeutic strategies to counteract formation of the tumor microenvironment and related processes leading to T cell exhaustion and repolarization of immunosuppressive tumor-associated macrophages.

scholarly journals TUMOR CELL ABUNDANCE IN CLASSIC HODGKIN LYMPHOMA

2019 ◽  
pp. 1-4
Author(s):  
Daniel Benharroch
Keyword(s):  
Tumor Cell ◽  
Cell Count ◽  
Hodgkin Lymphoma ◽  
Tumor Cells ◽  
Measles Virus ◽  
Indirect Evidence ◽  
Biological Properties ◽  
High Rate ◽  
Malignant Cells ◽  
Classic Hodgkin Lymphoma

OBJECTIVES: Study the relevance of a high proportion of tumor cells to the clinical and biological properties of classic Hodgkin lymphoma. METHODS: Tumor cells were counted in sections of the lymphoma stained with CD30,as this highlights the tumor cells of this neoplasm.We assessed abundant malignant cells (≥99 cells/10 high power fields) as the median count of tumor cells. RESULTS: A wealth of tumor cells was detected in 61 (52.1%) patients, in contrast with 56 (47.9%) patients with a low count.No clinical variance was found between cases rich or poor in malignant cells,except for a statistically significant preference of a high rate of tumor cells for female patients as well as for a high expression of measles virus antigens.The apoptotic tumor cell distribution showed no major disparity with the neoplasm characteristics. CONCLUSIONS: The entire type spectrum of Hodgkin lymphoma as evaluated by the tumor cell count has no direct bearing on the course of the lymphoma. But there might be indirect evidence for an association of a high tumor cell count,female preference,a strong expression of measles virus antigens and a poor prognosis

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 Hodgkin Reed–Sternberg-Like Cells in Non-Hodgkin Lymphoma

Diagnostics ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1019
Author(s):  
Paola Parente ◽  
Magda Zanelli ◽  
Francesca Sanguedolce ◽  
Luca Mastracci ◽  
Paolo Graziano
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Lineage ◽  
Clinicopathological Correlation ◽  
Therapeutic Approaches ◽  
Similar Morphology ◽  
Non Hodgkin Lymphoma ◽  
Classic Hodgkin Lymphoma ◽  
Lineage Markers ◽  
Small Clusters

Reed–Sternberg cells (RSCs) are hallmarks of classic Hodgkin lymphoma (cHL). However, cells with a similar morphology and immunophenotype, so-called Reed–Sternberg-like cells (RSLCs), are occasionally seen in both B cell and T cell non-Hodgkin Lymphomas (NHLs). In NHLs, RSLCs are usually present as scattered elements or in small clusters, and the typical background microenviroment of cHL is usually absent. Nevertheless, in NHLs, the phenotype of RSLCs is very similar to typical RSCs, staining positive for CD30 and EBV, and often for B cell lineage markers, and negative for CD45/LCA. Due to different therapeutic approaches and prognostication, it is mandatory to distinguish between cHL and NHLs. Herein, NHL types in which RSLCs can be detected along with clinicopathological correlation are described. Moreover, the main helpful clues in the differential diagnosis with cHL are summarized.

Local and systemic induction of CD4+CD25+ regulatory T-cell population by non-Hodgkin lymphoma

Blood ◽  
2008 ◽  
Vol 111 (11) ◽  
pp. 5359-5370 ◽  
Author(s):  
Sajjan Mittal ◽  
Neil A. Marshall ◽  
Linda Duncan ◽  
Dominic J. Culligan ◽  
Robert N. Barker ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Hodgkin Lymphoma ◽  
Tumor Cells ◽  
Cd4 T Cells ◽  
Mononuclear Cells ◽  
Treg Cells ◽  
Disease Stage ◽  
Serum Lactate Dehydrogenase ◽  
Non Hodgkin Lymphoma

Abstract Regulatory T (Treg) cells contribute to immune evasion by malignancies. To investigate their importance in non-Hodgkin lymphoma (NHL), we enumerated Treg cells in peripheral blood mononuclear cells (PBMCs) and involved tissues from 30 patients. CD25+FoxP3+CD127lowCD4+ Treg cells were increased markedly in PBMCs (median = 20.4% CD4 T cells, n = 20) versus healthy controls (median = 3.2%, n = 13, P < .001) regardless of lymphoma subtype, and correlated with disease stage and serum lactate dehydrogenase (Rs = 0.79, P < .001). T-cell hyporesponsiveness was reversed by depleting CD25+ cells, or by adding anti–CTLA-4, supporting the view that Treg cells explain the systemic immunosuppression seen in NHL. A high proportion of Treg cells was also present in involved tissues (median = 38.8% CD4 T cells, n = 15) versus reactive nodes (median = 11.6%, n = 2, P = .02). When autologous CD25− PBMC fractions were incubated with tumor cells from patients (n = 6) in vitro, there was consistent strong induction and then expansion of cells with the CD4+CD25+FoxP3+ phenotype of classic “natural” Treg cells. This population was confirmed to be suppressive in function. Direct cell-cell interaction of tumor cells with CD25− PBMCs was important in Treg induction, although there was heterogeneity in the mechanisms responsible. We conclude that NHL cells are powerful inducers of Treg cells, which may represent a new therapeutic target.

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.

Potent and specific antitumor effects of an anti-CD22–targeted cytotoxic ribonuclease: potential for the treatment of non-Hodgkin lymphoma

Blood ◽  
2001 ◽  
Vol 97 (2) ◽  
pp. 528-535 ◽  
Author(s):  
Dianne L. Newton ◽  
Hans J. Hansen ◽  
Stanislaw M. Mikulski ◽  
David M. Goldenberg ◽  
Susanna M. Rybak
Keyword(s):  
Life Span ◽  
Hodgkin Lymphoma ◽  
Tumor Cells ◽  
B Cell Lymphoma ◽  
Rnase A ◽  
Antitumor Effects ◽  
Non Hodgkin Lymphoma ◽  
Daudi Cells ◽  
Covalently Linked

Abstract LL2, an anti-CD22 monoclonal antibody against B-cell lymphoma, was covalently linked to the amphibian ribonuclease, onconase, a member of the pancreatic RNase A superfamily. LL2 increased in vitro potency (10 000-fold) and specificity against human Daudi Burkitt lymphoma cells while decreasing systemic toxicity of onconase. Monensin further increased potency of LL2-onconase on Daudi cells (IC50, 20 and 1.5 pM, absence and presence of monensin, respectively). A 1-hour exposure to LL2-onconase was sufficient to kill Daudi cells in culture. These favorable in vitro properties translated to significant antitumor activity against disseminated Daudi lymphoma in mice with severe combined immunodeficiency disease. In mice inoculated with tumor cells intraperitoneally (ip), LL2-onconase (100 μg 5 times ip every day) increased the life span of animals with minimal disease 200%. The life span of mice with advanced disseminated Daudi lymphoma (tumor cells inoculated intravenously) was increased 135%. Mice injected with LL2-onconase tolerated a dose as high as 300 mg/kg. Because both onconase and LL2 are in clinical trials as cancer therapeutics, the covalently linked agents should be considered for treatment of non-Hodgkin lymphoma.

Expression of complement inhibitors CD46, CD55, and CD59 on tumor cells does not predict clinical outcome after rituximab treatment in follicular non-Hodgkin lymphoma

Blood ◽  
2001 ◽  
Vol 98 (5) ◽  
pp. 1352-1357 ◽  
Author(s):  
Wen-Kai Weng ◽  
Ronald Levy
Keyword(s):  
Clinical Outcome ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Tumor Cells ◽  
Antitumor Effect ◽  
Non Hodgkin Lymphoma ◽  
Complement Inhibitors ◽  
Response Groups

Rituximab is a chimeric monoclonal antibody that targets B-cell–specific antigen CD20 and an effective treatment for B-cell non-Hodgkin lymphoma. Although it is readily used in clinical practice, the exact mechanism of its antitumor effect is unclear. One potential mechanism involves complement-mediated cytotoxicity. It has been shown that rituximab induces complement-mediated cytotoxicity in follicular lymphoma cells in vitro, and complement inhibitors CD55 and CD59 may regulate this process. To determine whether complement inhibitors play a role in regulating the antitumor effect of rituximab, the expression of complement inhibitors CD46, CD55, and CD59 was analyzed in pretreatment tumor cells from 29 rituximab-treated follicular lymphoma patients. Among them, 8 patients achieved complete responses, 11 patients achieved partial responses, and 10 patients showed no or minimal responses to rituximab treatment. Expression of surface CD20, CD46, CD55, and CD59 was determined by 2-color flow cytometry. Although the CD59 level was slightly lower in the complete response group, there was no statistically significant difference in the expression of individual complement inhibitor CD46 (mean channel fluorescence [MCF]: NR, 26.4; PR, 21.9; CR, 29.9), CD55 (MCF: NR, 16.4; PR, 14.9; CR, 23.2), or CD59 (MCF: NR, 41.6; PR, 40.6; CR, 30.6), the combination of any 2 inhibitors, or all 3 on tumor cells from 3 response groups. In addition, there was no difference in the rituximab-induced complement-mediated cytotoxicity in an in vitro assay using tumor cells from 3 response groups. Thus, CD46, CD55, and CD59 expression on pretreatment tumor cells, or their susceptibility to in vitro complement-mediated killing, does not predict clinical outcome after rituximab treatment.

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