Schematic representation of the reciprocal contribution of mast cells (MC), effector T cells (Teff), and regulatory T cells (Treg) to the HL-associated immunological microenvironment. (a) Mast cells, as other innate immune players directly sustain RS cell proliferation and proinflammatory mediator synthesis. (b) This effect is boosted by Teff that contributes to mast cell activation and amplifies the inflammatory spur. (c) Treg can interfere with the activation status of both Teff and MC through the OX40/OX40L axis and TGF-β release eventually limiting the delivery of the proliferation/survival signal to RS cells. (d) However, when the microenvironment is diverted towards marked inflammation owing to the abundant presence of activated MC, the regulatory function of Treg may prove inadequate to restore the balance between pro- and anti-inflammatory stimuli, and Treg can even boost inflammation through TGF-β release and Th17 generation.
