Abstract
Tumor necrosis factor α (TNF) is a potent pro-inflammatory cytokine that has deleterious effect in some autoimmune diseases, which led to the use of anti-TNF drugs in some of these diseases. However, some rare patients treated with these drugs paradoxically develop an aggravation of their disease or new onset autoimmunity, revealing an immunosuppressive facet of TNF. A possible mechanism of this observation is the direct and positive effect of TNF on regulatory T cells (Tregs) through its binding to the TNF receptor type 2 (TNFR2). Indeed, TNF is able to increase expansion, stability, and possibly function of Tregs via TNFR2. In this review, we discuss the role of TNF in graft-versus-host disease as an example of the ambivalence of this cytokine in the pathophysiology of an immunopathology, highlighting the therapeutic potential of triggering TNFR2 to boost Treg expansion. We also describe new targets in immunotherapy of cancer, emphasizing on the putative suppressive effect of TNF in antitumor immunity and of the interest of blocking TNFR2 to regulate the Treg compartment.
Highlights
Specialty section: This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology
Tumor necrosis factor α binds to two receptors, namely, TNF receptor type 1 (TNFR1) and TNFR2 (Figure 1)
Tumor necrosis factor α plays a key role in acute graft-versus-host disease (GVHD), a systemic and highly inflammatory complication that occurs after allogeneic hematopoietic stem cell transplantation [45]
Summary
Tumor necrosis factor α (TNF) is a potent pro-inflammatory cytokine that has deleterious effect in some autoimmune diseases, which led to the use of anti-TNF drugs in some of these diseases. We discuss the role of TNF in graft-versus-host disease as an example of the ambivalence of this cytokine in the pathophysiology of an immunopathology, highlighting the therapeutic potential of triggering TNFR2 to boost Treg expansion. Tumor necrosis factor α is a pleiotropic cytokine produced by various cell types and involved in a wide range of pathological processes [for review, see Ref [1, 2]]. It has been initially considered as a pro-inflammatory molecule. We will describe below in detail the case of graft-versus-host disease (GVHD) as an example of the ambivalent action of TNF in an immunopathology
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