Abstract MIP-068: TUMOR–PROMOTING EFFECTS OF THE OVARIAN CANCER MUCIN, MUC16, ARE ASSOCIATED WITH SUPPRESSION OF INNATE IMMUNITY

Abstract

Abstract The membrane-spanning mucin MUC16 promotes proliferation and metastasis of ovarian cancer cells. Here, we demonstrate that mice implanted with MUC16-knockdown human ovarian tumors show greater than two-fold increase in survival as compared to controls with tumors that express this mucin. While the lower survival of mice bearing MUC16-positive tumors is reportedly attributable to the ability of MUC16 to increase proliferation and metastasis, we also show that murine NK cells and macrophages are more efficient at lysing MUC16-knockdown cells. Macrophages showed infiltration in the MUC16-knockdown tumors but were restricted to the surrounding stroma in MUC16-positive tumors. In vitro cytotoxicity assays with NK cells and macrophages isolated from mice stimulated with agonistic anti-CD40 antibody showed 2-3-fold increased activity against the MUC16-knockdown cells as compared to matching target cells expressing this mucin. Finally, knockdown of MUC16 increased the susceptibility of cancer cells to ADCC and lysis by KS-IL2, an immunocytokine investigated as a treatment for ovarian cancer. Collectively our results support a role for MUC16 in promoting tumor growth. The ability of murine innate cells to selectively target MUC16-knockdown cells indicates that in vivo experiments investigating the biology of this mucin should be interpreted taking into account its immunomodulating activity as well as its growth promoting properties. Citation Format: Mildred Felder, Arvinder Kapur, Alexander L. Rakhmilevich, Xiaoyi Qu2, Joseph Connor, and Manish S. Patankar. TUMOR–PROMOTING EFFECTS OF THE OVARIAN CANCER MUCIN, MUC16, ARE ASSOCIATED WITH SUPPRESSION OF INNATE IMMUNITY [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr MIP-068.