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

Caroline Kreuzinger 1 Angelika Geroldinger 2 Dominiek Smeets 3 Elena Ioana Braicu 4 Jalid Sehouli 5, 4 Julia Koller 6 Andrea Wolf Silvia Darb-Esfahani 7, 4 Korinna Joehrens 4 Ignace Vergote 8, 9 Adriaan Vanderstichele 10 Bram Boeckx 11 Diether Lambrechts 11 Hani Gabra 12 G. Bea A. Wisman 13 Fabian Trillsch 14 Georg Heinze 15 Reinhard Horvat 16 Stephan Polterauer 1 Els Berns 17 Charles Theillet 18 Dan Cacsire Castillo-Tong 6
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 while 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 to the silent ones. Conclusion: 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.
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Contributeur : Nathalie Salvy-Cordoba <>
Soumis le : jeudi 5 septembre 2019 - 11:53:59
Dernière modification le : vendredi 6 septembre 2019 - 01:23:11

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Caroline Kreuzinger, Angelika Geroldinger, Dominiek Smeets, Elena Ioana Braicu, Jalid Sehouli, et al.. A Complex Network of Tumor Microenvironment in Human High-Grade Serous Ovarian Cancer. Clinical Cancer Research, American Association for Cancer Research, 2017, 23 (24), pp.7621-7632. ⟨10.1158/1078-0432.CCR-17-1159⟩. ⟨hal-02279442⟩



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