Tumor Necrosis Factor α and Regulatory T Cells in Oncoimmunology

Frontiers in Immunology

Jimena Tosello¹  Eliane Piaggio¹  José L. Cohen²  Mathieu Leclerc³  Benoît L. Salomon⁴  Emilie Ronin⁴ 

[1] Center of Cancer Immunotherapy and Centre d’Investigation Clinique Biothérapie 1428, Institut Curie, PSL Research University, INSERM U932, Paris, France;Centre d’Investigation Clinique Biothérapie, Assistance Publique Hôpitaux de Paris (APHP), Hôpital H. Mondor, Créteil, France;Service d’Hématologie Clinique et de Thérapie Cellulaire, Assistance Publique Hôpitaux de Paris (APHP), Hôpital H. Mondor, Créteil, France;Sorbonne Université, INSERM, CNRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France;Université Paris-Est and INSERM U955, Créteil, France;

关键词: tumor necrosis factor α;    TNFR2;    regulatory T cells;    cancer;    graft-versus-host disease;    immunotherapy;   

DOI  :  10.3389/fimmu.2018.00444

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown