Abstract 2748: Impact of ARID1A mutation on the tumor microenvironment of advanced clear cell ovarian cancer

Treatment of advanced Clear Cell Ovarian Cancer (CCOC) with immune checkpoint inhibition (ICI) is currently undergoing evaluation in a Phase II clinical trial. ARID1A mutations, which occur in up to 57% of CCOC, influence immune cell infiltration in pre-clinical models, but more information is needed on how it alters the tumor microenvironment (TME) of human CCOC. Methods: FFPE samples from 36 cases of FIGO III-IV CCOC were analyzed. Of the 36 cases; 21 were ARID1A wildtype (ARID1Awt), 14 ARID1A mutant (ARID1Amut) and 1 mixed. Immunohistochemistry was performed for immune markers (CD3, CD8, CD4, CD45RO, FOXP3, CD20, CD68, CD1a, Mast Cell Tryptase, Eosinophil Derived Neurotoxin, alpha-SMA) alongside PD1, PDL1, PDL2 and quantified using QuPath. The malignant cell area (MCA), leading edge (LE) and stroma were measured separately to provide information on immune marker location within the TME. Collagen was identified by Masson's Trichrome with structural analysis using the FIJI plugin TWOMBLI. Statistical analysis was performed on PRISM. Results: In this study we found significant differences between the TME of ARID1Awt and ARID1Amut tumors in terms of both immune infiltrate, collagen density and structure. ARID1Awt tumors had more collagen, with longer fibers and more branchpoints across the MCA, LE and Stroma (