Reed-Sternberg cell microenvironment in classical Hodgkin lymphoma — pathogenetic role and therapeutic target

Abstract

Classical Hodgkin lymphoma (cHL) is characterized by pathognomonic Reed-Sternberg (R-S) cells, surrounded by an extensive infiltrate of T- and B-lymphocytes, granulocytes, macrophages, plasma cells, eosinophils, mast cells and fibroblasts. This peculiar infiltrate exhibits profound local immunosuppressive properties and extensive network of mutual connections with R-S cells. Chemokines, cytokines and immunomodulatory proteins produced and released by R-S cells directly skew T-cell compartment toward Th2 and Treg cells, and induce infiltration of other cellular components that support R-S cell proliferation. Microenvironment-induced activation of R-S cell surface tumor necrosis factor-family receptors, cytokine receptors and Notch-1 signaling trigger activation of transcription nuclear factor kB (NFkB), JAK–STAT axis and suppression of B-cell transcriptional program. Understanding of these complex relationships led to conceptual design of targeted therapeutic interventions that by selective inhibition of receptor signaling, depletion of microenvironment cellular components or immunomo-dulation can deprive R-S cells from their supportive niche and complement conventional chemotherapy or R-S-cell-targeted drugs. The presented manuscript summarizes current views on the role of microenvironment in cHL, emphasizes its potential therapeutic applications.
Hematologia 2011; 2, 1: 1–14