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

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Title: A Complex Network of Tumor Microenvironment in Human High-Grade Serous Ovarian Cancer.
Author(s): Kreuzinger, C
Geroldinger, A
Smeets, D
Braicu, EI
Sehouli, J
Koller, J
Wolf, A
Darb-Esfahani, S
Joehrens, K
Vergote, I
Vanderstichele, A
Boeckx, B
Lambrechts, D
Gabra, H
Wisman, GBA
Trillsch, F
Heinze, G
Horvat, R
Polterauer, S
Berns, E
Theillet, C
Cacsire Castillo-Tong, D
Item Type: Journal Article
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; 1-12. ©2017 AACR.
Publication Date: 2-Oct-2017
Date of Acceptance: 27-Sep-2017
URI: http://hdl.handle.net/10044/1/55181
DOI: https://dx.doi.org/10.1158/1078-0432.CCR-17-1159
ISSN: 1078-0432
Publisher: American Association for Cancer Research
Start Page: 7621
End Page: 7632
Journal / Book Title: Clinical Cancer Research
Volume: 23
Issue: 24
Copyright Statement: ©2017 American Association for Cancer Research
Sponsor/Funder: Commission of the European Communities
Funder's Grant Number: 279113
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
INFILTRATING LYMPHOCYTES
EXTRACELLULAR-MATRIX
CELL INFILTRATION
PD-L1 EXPRESSION
T-CELLS
CARCINOMA
IMMUNOTHERAPY
EVOLUTION
METASTASIS
RESISTANCE
1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status: Published
Embargo Date: 2018-10-02
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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