Characterizing the role of IL-33/ST2 axis in regulating anti-tumor function by CD8 T cells during tumor metastasis in the omentum.

Abstract

Abstract The omentum, a visceral adipose tissue, is a frequent site of metastasis for gastric and ovarian cancers. Advanced ovarian cancer almost always metastasizes to the omentum. Currently available therapies do not control tumor growth long-term and there is a frequent recurrence of tumor metastasis. In mice, tumor cells injected intraperitoneally implant in the omentum and grow progressively despite tumor-specific CD8 T cells. The lack of effective immunity is due in part, to rapid Treg recruitment in the omentum, which provides an immunosuppressive environment to support tumor growth. The Tregs in the omentum are a specialized population called visceral adipose tissue associated Tregs (VAT-Tregs). A portion of the omental VAT-associated Tregs express ST2, a receptor for Interleukin-33 (IL-33), suggesting that local IL-33 production may contribute to Treg-mediated suppression in the omentum. We also detected persistent, continuously expanding, tumor-specific CD8 T cells in the omentum. Given that IL-33 can also enhance effector function by CD8 T cells and promote their persistence in the presence of chronic antigen stimulation, we are investigating how IL-33 regulates the balance of Treg-mediated immune-suppression and CD8-mediated tumor cell killing in the context of omental adipose tissue. R01CA216234