PRKCI promotes immune suppression in ovarian cancer through YAP1

A key feature of high-grade serous ovarian carcinoma (HGSOC) is frequent amplification of the 3q26 locus harboring PRKC-iota (PRKCI). Here, we show that PRKCI is also expressed in early fallopian tube lesions, called Serous Tubal Intraepithelial Carcinoma. Transgenic mouse studies establish PRKCI as an ovarian cancer specific oncogene and system level and functional analyses identify YAP1 as a downstream effector in tumor progression. Mechanistically, the oncogenic activity of the PRKCI-YAP1 axis relates in part to the upregulation of TNF to promote an immune suppressive tumor microenvironment characterized by an abundance of myeloid-derived suppressor cells and inhibition of cytotoxic T cell infiltration. In human ovarian cancers, high PRKCI expression also correlates with high expression of YAP1 and low infiltration of cytotoxic T-cell. The PRKCI-YAP1 regulation of the tumor immunity provides a therapeutic strategy for highly lethal ovarian cancer.

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