The Tumor Microenvironment of Clear-Cell Ovarian Cancer

Devlin, MJ; Miller, R; Laforets, F; Kotantaki, P; Garsed, DW; Kristeleit, R; Bowtell, DD; McDermott, J; Maniati, E; Balkwill, FR

Author(s): Devlin, MJ; Miller, R; Laforets, F; Kotantaki, P; Garsed, DW; Kristeleit, R; Bowtell, DD; McDermott, J; Maniati, E; Balkwill, FR;
Details: Publication Year 2022-11-02,Volume 10,Issue #11,Page 1326-1339
Journal Title: Cancer Immunology Research
Publication Type: Research article
Abstract: Some patients with advanced clear-cell ovarian cancer (CCOC) respond to immunotherapy; however, little is known about the tumor microenvironment (TME) of this relatively rare disease. Here, we describe a comprehensive quantitative and topographical analysis of biopsies from 45 patients, 9 with Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stage I/II (early CCOC) and 36 with FIGO stage III/IV (advanced CCOC). We investigated 14 immune cell phenotype markers, PD-1 and ligands, and collagen structure and texture. We interrogated a microarray data set from a second cohort of 29 patients and compared the TMEs of ARID1A-wildtype (ARID1Awt) versus ARID1A-mutant (ARID1Amut) disease. We found significant variations in immune cell frequency and phenotype, checkpoint expression, and collagen matrix between the malignant cell area (MCA), leading edge (LE), and stroma. The MCA had the largest population of CD138+ plasma cells, the LE had more CD20+ B cells and T cells, whereas the stroma had more mast cells and alphaSMA+ fibroblasts. PD-L2 was expressed predominantly on malignant cells and was the dominant PD-1 ligand. Compared with early CCOC, advanced-stage disease had significantly more fibroblasts and a more complex collagen matrix, with microarray analysis indicating "TGFbeta remodeling of the extracellular matrix" as the most significantly enriched pathway. Data showed significant differences in immune cell populations, collagen matrix, and cytokine expression between ARID1Awt and ARID1Amut CCOC, which may reflect different paths of tumorigenesis and the relationship to endometriosis. Increased infiltration of CD8+ T cells within the MCA and CD4+ T cells at the LE and stroma significantly associated with decreased overall survival.
Keywords: Female; Humans; *Tumor Microenvironment; Programmed Cell Death 1 Receptor; CD8-Positive T-Lymphocytes; *Ovarian Neoplasms/pathology; Collagen
Department(s): Laboratory Research
PubMed ID: 36095166
Publisher's Version: https://doi.org/10.1158/2326-6066.CIR-22-0407
Open Access at Publisher's Site: https://doi.org/10.1158/2326-6066.CIR-22-0407
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-10-23 06:31:36

Last Modified: 2024-10-23 06:33:16