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Hodgkin’s disease: A disorder of dysregulated cellular cross-talk

  • Published:
Biotherapy

Abstract

Hodgkin’s disease (HD) is a peculiar type of human malignant lymphoma characterized by a very low frequency of tumor cells, the so called Hodgkin and Reed-Sternberg (H-RS) cells, embedded in a hyperplastic background of non-neoplastic (reactive) cells recruited and activated by H-RS cells-derived cytokines. H-RS cells can be functionally regarded as antigen-presenting cells (APC) able to elicit an intense, but anergic and ineffective, T-cell mediated immune response along with a hyperplastic inflammatory reaction which involves several cell types including T- and B-cells, neutrophils, eosinophils, plasma cells, fibroblasts and stromal cells. In tissues involved by HD, malignant H-RS cells and their reactive neighboring cells are able to cross-talk via a complex network of cytokine- and cell contact-dependent interactions. As a result of such interactions, mediated by specific surface receptors and adhesion molecules on both tumor and non-neoplastic cells, H-RS cells may receive several proliferative and anti-apoptotic signals favoring the cellular expansion and tumor cell survival in HD. The ineffective T-cell immune response elicited by the abnormal APC function of H-RS cells may further contribute to the biologic and clinical progression of HD. Innovative therapeutic strategies aimed at blocking the pathways of dysregulated cellular cross-talk among H-RS cells and bystander reactive cell populations might be beneficial in the treatment of HD patients.

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Abbreviations

APC:

antigen presenting cell

CD:

cluster of differentiation

EBV:

Epstein-Barr virus

EMA:

epithelial membrane antigen

GM-CSF:

granulocyte-macrophage colony-stimulating factor

HD:

Hodgkin’s disease

HIV:

human immunodeficiency virus

H-RS:

Hodgkin and Reed-Sternberg cell

HTLV:

human T cell leukemia virus

ICAM-1:

intercellular adhesion molecule-1

IFN-γ:

interferon-γ

Ig:

immunoglobulin

IL:

interleukin

L:

ligand

LD:

lymphocyte depletion

LFA-1:

leukocyte function antigen-1

LIF:

leukemia inhibitory factor

LP:

lymphocyte predominance

LT-α:

lymphotoxin-α

MC:

mixed cellularity

M-CSF:

macrophage colony-stimulating factor

MHC:

major histocompatibility complex

NGF:

nerve growth factor

NHL:

non-Hodgkin lymphoma

NS:

nodular sclerosis

PCR:

polymerase chain reaction

R:

receptor

RANTES:

regulated upon activation normal T cell, expressed and secreted

SCF:

stem cell factor

TCR:

T cell receptor

TGF-β:

transforming growth factor-β

TNF:

tumor necrosis factor

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Authors and Affiliations

  1. The Leukemia Unit, Department of Medical Oncology, Centro Regionale di Riferimento Oncologico, IRCCS, Via Pedemontana Occidentale, I-33081, Aviano, Italy

    Antonio Pinto, Valter Gattei, Donatella Aldinucci, Massimo Degan, Angela De Iuliis, Francesca Maria Rossi, Francesca Tassan Mazzocco, Cristiana Godeas & Dalisa Poletto

  2. Department of Medical Oncology, I.R.C.C.S., I-33081, Aviano, Italy, Italy

    Vittorina Zagonel & Maurizio Rupolo

  3. Pathology Centro di Riferimento Oncologico, I.R.C.C.S., I-33081, Aviano, Italy

    Annunziata Gloghini & Antonino Carbone

  4. Department of Hematology and Oncology, Internal Medicine III, Medical Center of the University of Ulm, Germany

    Hans-Jürgen Gruss

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  1. Antonio Pinto
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  2. Valter Gattei
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  3. Vittorina Zagonel
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  13. Antonino Carbone
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  14. Hans-Jürgen Gruss
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Corresponding author

Correspondence to Antonio Pinto.

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Supported by the Associazione Italiana per la Ricerca sul Cancro; the Associazione Italiana contro le Leucemie, ‘Trenta ore per la vita’ and the Ministero della Sanità, Ricerca Finalizzata I.R.C.C.S., Italy.

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Pinto, A., Gattei, V., Zagonel, V. et al. Hodgkin’s disease: A disorder of dysregulated cellular cross-talk. Biotherapy 10, 309–320 (1998). https://doi.org/10.1007/BF02678551

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