Spotlight on Nuclear PD-L1 in Ovarian Cancer Chemoresistance: Hidden but Mighty

Meshach Asare-Werehene¹Arvin Zaker²Shivanshi Tripathi²Laudine Communal³Euridice Carmona³Anne-Marie Mes-Masson³Benjamin Tsang¹Arvind Mer^2*

• ¹Department of Obstetrics & Gynecology, University of Ottawa, Ottawa, Canada
• ²Department of Biochemistry, Immunology and Microbiology, University of Ottawa, Ottawa, Canada
• ³University of Montreal Hospital Centre (CRCHUM), Montreal, Quebec, Canada

Ovarian cancer (OVCA) has a 5-year survival rate of ~45% with no significant survival improvement in the last 30 years. Late diagnosis and chemoresistance have been a major obstacle to therapeutic success. Anti-PD-L1 has achieved only a modest therapeutic success in OVCA despite significant therapeutic responses in other solid cancers. These treatments only inhibit the membranal and soluble isoforms of PD-L1 without targeting the nuclear isoform. Little is known about nuclear PD-L1 and its role in OVCA chemoresistance. Here, we report on the prognostic impact of nuclear PD-L1 and its interaction with plasma gelsolin (pGSN) and CD8+ T cells in the tumor microenvironment.Increased nuclear PD-L1 was associated with disease recurrence, chemoresistance and poor overall survival. Although CD8+ T cells provided survival benefits to patients, elevated PD-L1 hindered these benefits resulting in shortened disease free (DFS) and overall survival (OS). Co-expression of PD-L1 and pGSN was also associated with shortened DFS, OS and chemoresistance. These findings support our hypothesis that nuclear PD-L1 is a poor prognostic marker of tumor recurrence, chemoresistance and shortened overall survival.