P-01.07 The role of PP2Ac in regulating immune evasion in high grade serous ovarian cancer

<h3>Background</h3> High-grade serous ovarian cancer (HGSOC) is one of the most malignant gynaecological cancer types, with a 5-year survival rate of less than 30%.¹ Mechanisms to overcome tumor-associated immunosuppression in HGSOC have yet to be addressed. Protein phosphatase 2A catalytic subunit (PP2Ac) is the catalytic subunit of the PP2A complex. Emerging evidence suggests that PP2Ac activity impairs DNA damage response and facilitates immune evasion by negatively regulating the cGAS-STING signaling pathway in glioblastoma.² The function and therapeutic potential of PP2Ac inhibition in HGSOC remain elusive. <h3>Materials and Methods</h3> CRISPR/Cas9 was used to generate a PP2Ac-knockout mouse syngeneic ovarian cancer cell line (HGS1), and the knockout efficiency was confirmed by western blot. Functional assays were performed to assess cellular viability and proliferation. Additionally, total RNA was extracted from wild-type and PP2Ac-knockout cells, and RT-PCR was performed to measure the expression of three STING pathway genes (CXCL10, IRF7, and ISG15)³ in PP2AcKO cells. <h3>Results</h3> PP2Ac deficiency led to significantly reduced proliferation in ovarian cancer cells and upregulated MHC-I levels. Using RT-PCR, we further confirmed that the expression of three STING pathway genes (CXCL10, IRF7, and ISG15) was upregulated in PP2AcKO cells. <h3>Conclusions</h3> These findings demonstrate that PP2Ac deficiency can enhance ovarian cancer immunogenicity through increased antigen presentation. <h3>References</h3> Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, Gaudet MM, Jemal A, Siegel RL. Ovarian cancer statistics, 2018. <i>CA Cancer J Clin</i>. 2018;<b>68</b>(4):284–296. doi: 10.3322/caac.21456 Cai J, Liu T, Huang P, <i>et al</i>. Protein phosphatase 2A mediates immune evasion in glioblastoma by negative regulation of the cGAS-STING pathway. <i>Sci Transl Med.</i> 2021;<b>13</b>(625):eabe1721. doi: 10.1126/scitranslmed.abe1721 Ishikawa H, Barber GN. STING signaling pathway and regulation of innate immune signaling in cancer. <i>Nat Rev Immunol.</i> 2022;<b>22</b>(3):164–179. doi: 10.1038/s41577-021-00627-1 X. He: None. R. Long: None. R. Zhang: None. C. Cui: None. M. Siu: None. K. Liu: None. R. Lu: None. H. Lu: None. K. Chan: None.