Theme 2: Immune tolerance and T-cell function

Overview:  CD4+ helper T cells mediate cellular immunity and tissue inflammation as well as help the activation of B cells and CD8+ T cells. CD8+ cytotoxic T cells (CTLs) function as important anti-tumor effector cells in addition to mediating anti-viral immunity. Immunosuppressive regulatory T (Treg) cells function to maintain normal immune homeostasis and prevent autoimmunity; however, this population of T cells also hampers anti-tumor immunity. Thus, several CCIR members continue to study the development, function and homeostasis of different T cell subsets in order to find ways to manipulate the adaptive immune system for improving the efficacy of cancer immunotherapy.

Some highlights from the past year include:  
• 4-1BB agonist antibody treatment induces a population of KLRG1+ T cells that infiltrate melanoma tumors and investigation of the origin and function of these cells, as well as their place within established T cell paradigms revealed that these T cells, particularly the CD4 lineage, represent a novel phenotype characterized by enhanced, multipotent cytotoxicity; this novel phenotype resolves multiple questions associated with 4-1BB activation, including how 4-1BB enhances tumor-specific cytotoxicity and how 4-1BB can promote tumor immunity while repressing autoimmunity (Curran MA, J Exp Med. 2013)

Additional Relevant Publications: