Do CD4+ CD25+ immunoregulatory T cells hinder tumor immunotherapy?
After years of banishment from mainstream immunology, the notion that one subset of T cells can exert regulatory effects on other T lymphocytes is back in fashion. Recent work in knockout and transgenic mice has begun to bring molecular definition to our understanding of immunoregulatory CD4+CD25+ T cells (Treg/Th3/Tr1). The identification of the glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR, also known as TNFRSF18) expressed on T regulatory cells might afford new therapeutic opportunities. Another possible therapeutic intervention could be the blockade of signaling through the molecular pair of tumor necrosis factor-related activation induced cytokine (TRANCE) and receptor activator of NF-kappaB (RANK). Based on the available evidence from experimental mouse tumor models, however, it seems that simply blocking or even eliminating T regulatory function will not be enough to manage established tumors. The challenge for immunotherapists now is to overcome immunosuppression using the knowledge gained through the understanding of T regulatory cell function.
Antony
Paul Andrew
PA
Surgery Branch, National Cancer Institute, Building 10, Room 2B42, 9000 Rockville Pike, Bethesda, MD 20892, USA. paul_antony@nih.gov
Restifo
Nicholas P
NP
D000818:Animals; D015551:Autoimmunity; D015704:CD4 Antigens / Q000032:analysis / Q000502:physiology*; D007108:Immune Tolerance; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
D015704:CD4 Antigens; D015375:Receptors, Interleukin-2