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

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  • Adam Makka
    Department of Microbial, Cellular and Molecular Biology, College of Natural Sciences, Addis Ababa University, Addis Ababa, Ethiopia, Armauer Hansen Research Institute, Addis Ababa, Ethiopia, Department of Oncology, Faculty of Medicine, Lund University, Lund, Sweden, Yirgalem Hospital Medical College, Yirgalem, Ethiopia,
  • Bekuretsion Yonas
    Department of Pathology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia,
  • Gebremedhin Amha
    Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia,
  • Kwiecinska Anna
    Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden
  • Howe Rawleigh
    Armauer Hansen Research Institute, Addis Ababa, Ethiopia,
  • Petros Beyene
    Department of Microbial, Cellular and Molecular Biology, College of Natural Sciences, Addis Ababa University, Addis Ababa, Ethiopia,
  • Jerkeman Mats
    Department of Oncology, Faculty of Medicine, Lund University, Lund, Sweden,

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<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 <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 mechanisms, 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>

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