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Evidence for distinct mechanisms of immune suppression in EBV-positive and EBV-negative Hodgkin lymphoma

Adam, Makka LU ; Bekuretsion, Yonas ; Gebremedhin, Amha ; Kwiecinska, Anna ; Howe, Rawleigh ; Petros, Beyene and Jerkeman, Mats LU (2023) In Journal of Clinical and Experimental Hematopathology 63(4). p.230-239
Abstract

Epstein Barr Virus (EBV) has been recognized for its ability to transform B lymphocytes and for its association with different types of cancers including Hodgkin lymphoma. In addition, EBV may also modulate the microenvironment of HL. In this study, we aimed to investigate the prevalence of EBV among HL cases in Ethiopia and to assess the tissue cellular composition of EBV-related and EBV-unrelated cases. We constructed a tissue microarray (TMA) of 126 consecutive cases of classical HL (CHL) and nodular lymphocyte predominant HL (NLPHL) from a tertiary cancer centre, Tikur Anbessa Hospital, Addis Ababa, Ethiopia, and evaluated a panel of immunohistochemical markers. The quantification of immune cells was performed using HALO 2.3, a... (More)

Epstein Barr Virus (EBV) has been recognized for its ability to transform B lymphocytes and for its association with different types of cancers including Hodgkin lymphoma. In addition, EBV may also modulate the microenvironment of HL. In this study, we aimed to investigate the prevalence of EBV among HL cases in Ethiopia and to assess the tissue cellular composition of EBV-related and EBV-unrelated cases. We constructed a tissue microarray (TMA) of 126 consecutive cases of classical HL (CHL) and nodular lymphocyte predominant HL (NLPHL) from a tertiary cancer centre, Tikur Anbessa Hospital, Addis Ababa, Ethiopia, and evaluated a panel of immunohistochemical markers. The quantification of immune cells was performed using HALO 2.3, a platform for image analysis from Indica Lab Inc. A total of 77/126 (61.1%) of HL cases expressed LMP1/EBER. Infiltration of CD8+, T-bet+ and FoxP3+ cells was higher in the microenvironment of EBV-related CHL, with P values of <0.001, <0.001 and <0.016, respectively. In contrast, the expression of PD1 was higher in the microenvironment of EBV-unrelated CHL cases (P < 0.001). Unlike in Western countries, the majority of HL cases in Ethiopia were associated with EBV. As FoxP3+ and PD1-expressing cells are thought to participate in down regulation of the immune response by different mecha-nisms, this finding highlights the previously unrecognized possibility that distinct immunosuppressive mechanisms may be ongoing within EBV positive and negative HL types. This may have important prognostic and therapeutic implications.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Epstein Barr Virus, HL microenvironment, immune suppression
in
Journal of Clinical and Experimental Hematopathology
volume
63
issue
4
pages
10 pages
publisher
Nihon Rinpa Monaikei Gakkai
external identifiers
  • pmid:38148013
  • scopus:85181199398
ISSN
1346-4280
DOI
10.3960/jslrt.23037
language
English
LU publication?
yes
id
aa63fcfa-1139-4116-82ce-ea816d462f36
date added to LUP
2024-02-01 11:20:13
date last changed
2024-04-17 21:18:25
@article{aa63fcfa-1139-4116-82ce-ea816d462f36,
  abstract     = {{<p>Epstein Barr Virus (EBV) has been recognized for its ability to transform B lymphocytes and for its association with different types of cancers including Hodgkin lymphoma. In addition, EBV may also modulate the microenvironment of HL. In this study, we aimed to investigate the prevalence of EBV among HL cases in Ethiopia and to assess the tissue cellular composition of EBV-related and EBV-unrelated cases. We constructed a tissue microarray (TMA) of 126 consecutive cases of classical HL (CHL) and nodular lymphocyte predominant HL (NLPHL) from a tertiary cancer centre, Tikur Anbessa Hospital, Addis Ababa, Ethiopia, and evaluated a panel of immunohistochemical markers. The quantification of immune cells was performed using HALO 2.3, a platform for image analysis from Indica Lab Inc. A total of 77/126 (61.1%) of HL cases expressed LMP1/EBER. Infiltration of CD8+, T-bet+ and FoxP3+ cells was higher in the microenvironment of EBV-related CHL, with P values of &lt;0.001, &lt;0.001 and &lt;0.016, respectively. In contrast, the expression of PD1 was higher in the microenvironment of EBV-unrelated CHL cases (P &lt; 0.001). Unlike in Western countries, the majority of HL cases in Ethiopia were associated with EBV. As FoxP3+ and PD1-expressing cells are thought to participate in down regulation of the immune response by different mecha-nisms, this finding highlights the previously unrecognized possibility that distinct immunosuppressive mechanisms may be ongoing within EBV positive and negative HL types. This may have important prognostic and therapeutic implications.</p>}},
  author       = {{Adam, Makka and Bekuretsion, Yonas and Gebremedhin, Amha and Kwiecinska, Anna and Howe, Rawleigh and Petros, Beyene and Jerkeman, Mats}},
  issn         = {{1346-4280}},
  keywords     = {{Epstein Barr Virus; HL microenvironment; immune suppression}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{230--239}},
  publisher    = {{Nihon Rinpa Monaikei Gakkai}},
  series       = {{Journal of Clinical and Experimental Hematopathology}},
  title        = {{Evidence for distinct mechanisms of immune suppression in EBV-positive and EBV-negative Hodgkin lymphoma}},
  url          = {{http://dx.doi.org/10.3960/jslrt.23037}},
  doi          = {{10.3960/jslrt.23037}},
  volume       = {{63}},
  year         = {{2023}},
}