A Complex Network of Tumor Microenvironment in Human High-Grade Serous Ovarian Cancer.

Abstract

Purpose: Most high-grade serous ovarian cancer (HGSOC) patients develop recurrent disease after first-line treatment, frequently with fatal outcome. This work aims at studying the molecular biology of both primary and recurrent HGSOC.Experimental Design: Gene expression profiles of matched primary and recurrent fresh-frozen tumor tissues from 66 HGSOC patients were obtained by RNA sequencing. Clustering analyses and pairwise comparison of the profiles between matched samples and subsequent functional alignment were used for the identification of molecular characteristics of HGSOC.Results: Both primary and recurrent HGSOC samples presented predominant gene expression differences in their microenvironment, determined by a panel of genes covering all major pathways of immune activation together with a number of genes involved in the remodeling of extracellular matrix and adipose tissues. Stratifying tumor tissues into immune active and silent groups, we further discovered that although some recurrent tumors shared the same immune status as their primary counterparts, others switched the immune status, either from silent to active or active to silent. Interestingly, genes belonging to the B7-CD28 immune checkpoint family, known for their major role as negative regulators of the immune response, were overexpressed in the immune active tumors. Searching for potential tumor antigens, CEACAM21, a member of the carcinoembryonic antigen family, was found to be significantly overexpressed in immune active tissues in comparison with the silent ones.Conclusions: The results illustrate the complexity of the tumor microenvironment in HGSOC and reveal the molecular relationship between primary and recurrent tumors, which have multiple therapeutic implications. Clin Cancer Res; 23(24); 7621-32. ©2017 AACR.

• Authors: Caroline Kreuzinger, Angelika Geroldinger, Dominiek Smeets, Elena Ioana Braicu, Jalid Sehouli, Julia Koller, Andrea Wolf, Silvia Darb-Esfahani, Korinna Joehrens, Ignace Vergote, Adriaan Vanderstichele, Bram Boeckx, Diether Lambrechts, Hani Gabra, G Bea A Wisman, Fabian Trillsch, Georg Heinze, Reinhard Horvat, Stephan Polterauer, Els Berns, Charles Theillet, Dan Cacsire Castillo-Tong
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 23 Issue 24 Pg. 7621-7632 (Dec 15 2017) ISSN: 1557-3265 [Electronic] United States
• PMID: 28972047 (Publication Type: Journal Article)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• Antigens, Neoplasm

Topics

• Adult
• Aged
• Antigens, Neoplasm (genetics, immunology)
• Cell Line, Tumor
• Cystadenocarcinoma, Serous (genetics, immunology, pathology)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Middle Aged
• Neoplasm Grading
• Neoplasm Recurrence, Local (genetics, pathology)
• Ovarian Neoplasms (genetics, immunology, pathology)
• Sequence Analysis, RNA
• Tumor Microenvironment (genetics, immunology)