In the Immunity study Meghan Turnis and colleagues from the Departments of Immunology at the University of Pittsburgh and the St. Jude Children’s Research Hospital, Memphis, TN demonstrate that the tumor microenvironment is characterized by a substantial enrichment of IL-35+ Treg cells.
According to the authors their results suggest that Treg cells are the major, and perhaps, the only source of IL-35 in the tumor microenvironment.
Importantly, the study indicates that the tumor-associated IL-35 contributes to reduced antigen-specific T cell infiltration, decreased effector immune function and memory, and increased tumor burden.
This is achieved mostly by the T-cell exhaustion in tumors, driven by IL-35, as the result of the increased expression of several inhibitory receptors such as PD1, TIM3 and LAG3.
The authors argue that their results may reveal an important and previously unrecognized mechanism for immune evasion – namely, the inflammatory milieu-mediated enrichment of IL-35+ Treg population within the tumor microenvironment.
According to the authors, it is highly likely that IL-35 is more prominently utilized as suppressive mechanism in cancer than in any other inflammatory or autoimmune disease or condition.