scholarly journals Plasma cells in classical Hodgkin lymphoma: a new player in the microenvironment?

2018 ◽  
Vol 184 (2) ◽  
pp. 119-120
Author(s):  
Lydia Visser
Keyword(s):  
Hodgkin Lymphoma ◽  
Plasma Cells ◽  
Classical Hodgkin Lymphoma

scholarly journals Revisiting IL-6 expression in the tumor microenvironment of classical Hodgkin lymphoma

2021 ◽  
Vol 5 (6) ◽  
pp. 1671-1681
Author(s):  
Alex Reza Gholiha ◽  
Peter Hollander ◽  
Ingrid Glimelius ◽  
Gustaf Hedstrom ◽  
Daniel Molin ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Hodgkin Lymphoma ◽  
Plasma Cells ◽  
Cox Regression ◽  
Tissue Microarrays ◽  
High Serum ◽  
Prognostic Impact ◽  
Classical Hodgkin Lymphoma ◽  
Programmed Death

Abstract Interleukin-6 (IL-6) can induce therapeutic resistance for several cancer agents currently used to treat classical Hodgkin lymphoma (cHL). We aimed to investigate whether the presence of IL-6+ leukocytes and IL-6+ Hodgkin-Reed-Sternberg (HRS) cells in the tumor microenvironment (TME) was associated with adverse survival outcomes, expression of other immune markers, and serum IL-6 levels. We used a contemporarily treated cohort (n = 136), with a median follow-up of 13.8 years (range, 0.59-15.9 years). We performed immunohistochemistry with an IL-6 antibody on tissue microarrays from diagnostic biopsies of cHL patients. Patients with IL-6+ leukocytes ≥1% (n = 54 of 136) had inferior event-free survival (hazard ratio [HR] = 3.58; 95% confidence interval [CI], 1.80-7.15) and overall survival (HR = 6.71; 95% CI, 2.51-17.99). The adverse survival was maintained in multivariate Cox regression and propensity score-matched analyses, adjusting for well-known poor-prognostic covariates. The presence of IL-6+ HRS cells and high serum IL-6 levels were not associated with survival. IL-6+ leukocytes correlated with increased proportions of IL-6+ HRS cells (P < .01), CD138+ plasma cells (P < .01), CD68+ macrophages (P = .02), and tryptase-positive mast cells (P < .01). IL-6+ HRS cells correlated with increased proportions of CD68+ macrophages (P = .03), programmed death-ligand 1–positive (PD-L1+) leukocytes (P = .04), and PD-L1+ HRS cells (P < .01). Serum-IL-6 lacked correlation with IL-6 expression in the TME. This is the first study highlighting the adverse prognostic impact of IL-6+ leukocytes in the TME in a cohort of contemporarily treated adult patients with cHL.

In Reed Sternberg Cells Suppression of the B-Cell Phenotype and Cell Proliferation Is Not Mediated by BLIMP-1.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 24-24
Author(s):  
Catherine Burton ◽  
Sharon Barrans ◽  
Gareth Williams ◽  
Bradley Dickinson ◽  
Reuben Tooze ◽  
...  
Keyword(s):  
Cell Cycle ◽  
B Cells ◽  
B Cell ◽  
Cell Cycle Arrest ◽  
Hodgkin Lymphoma ◽  
Tumour Cell ◽  
Plasma Cells ◽  
Cell Phenotype ◽  
Classical Hodgkin Lymphoma ◽  
Cycle Arrest

Abstract Expression of the transcriptional repressor BLIMP-1 is a pivotal event in the differentiation of post germinal centre B-cells to plasma cells. BLIMP-1 extinguishes the B-cell phenotype by down-regulation of PAX-5 with associated loss of BCL-6 and PU. and acting in concert with IRF-4 and XBP-1 induces the expression of the mature plasma cell phenotype. A key step in this process is the permanent exit of the differentiating plasma cell from the cell cycle which appears to be partly dependent on BLIMP-1 mediated repression of c-MYC. Reed Sternberg cells in Classical Hodgkin Lymphoma are known to be derived from post germinal centre B-cell which have undergone extinction of most elements of their B-cell phenotype but do not complete terminal differentiation to plasma cells. The primary aim of this study was to establish whether this loss of B-cell characteristics was mediated by BLIMP-1 and whether this was associated with exit from the cell cycle. 35 well characterised biopsies of nodular sclerosing Classical Hodgkin Lymphoma were studied using an extensive panel of B-cell and cell cycle markers. BLIMP-1 was identified using a BLIMP-1 alpha specific polyclonal antibody raised against the BLIMP-1 amino terminus which was validated by Western Blotting and immunocytochemical reactivity with normal plasma cells and squamous epithelia. All of the Reed Sternberg cells in all of the cases studied had the immunophenotype CD30+, IRF-4+, PU.1-. 15% cases showed PAX-5 a proportion of tumour cells and CD20 and or CD79 were found in 6% of cases. In 21% cases there was either nuclear or cytoplasmic expression of C/EBP alpha. All Reed Sternberg cells expressed Ki67 and around 50% of cells in all of the cases expressed the G2/M phase marker geminin with p53 and p21 uniformly expressed in the tumour cells. In contrast to the patterns seen in normal B-cell differentiation there was no evidence of BLIMP-1 or XBP-1 expression in any of the cases studied. To further clarify the reason for cell cycle arrest, interphase FISH using a panel of centromeric probes was performed on imprints preparations of lymph nodes replaced by Hodgkin lymphoma. This showed asymmetrical chromosome separation between the nuclear lobes of individual Reed Sternberg cells and heterogeneity of chromosome content within the mononuclear tumour cell fraction. These results indicate that extinction of the B-cell phenotype in Reed Sternberg cell is not dependent on the induction of BLIMP-1expression and that unlike B-cells undergoing differentiation to plasma cells most Reed Sternberg cells undergo cell cycle arrest mediated by normal p53 expression rather than permanently exiting from the cell cycle. Cell cycle arrest is likely to be related to asymmetrical chromosomal segregation within the tumour cell population. Previous experimental studies have shown that plasma cells differentiation is blocked in cells that are continuing to cycle. The results of this study raise the possibility that cell cycle arrest due to abberrant mitosis may be a key factor in determing the distinctive phenotype of Reed Sternberg cells through a mechansim that is independent of BLIMP-1 activation.

M2 Macrophages but not M1 Macrophages Are Associated with Worst Outcome in Classical Hodgkin Lymphoma

2014 ◽  
Vol 226 (02) ◽  
Author(s):  
M Barros ◽  
P Segges ◽  
G Vera-Lozada ◽  
R Hassan ◽  
G Niedobitek
Keyword(s):  
Hodgkin Lymphoma ◽  
M2 Macrophages ◽  
Classical Hodgkin Lymphoma ◽  
M1 Macrophages
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