Dynamics of the intratumoral immune response during progression of high-grade serous ovarian cancer

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Title: Dynamics of the intratumoral immune response during progression of high-grade serous ovarian cancer
Authors: Stanske, M
Wienert, S
Castillo-Tong, DC
Kreuzinger, C
Vergote, I
Lambrechts, S
Gabra, H
Gourley, C
Ganapathi, RN
Kolaschinski, I
Budczies, J
Sehouli, J
Ruscito, I
Denkert, C
Kulbe, H
Schmitt, W
Jöhrens, K
Braicu, I
Darb-Esfahani, S
Item Type: Journal Article
Abstract: PURPOSE: Tumor-infiltrating lymphocytes (TILs) have an established impact on the prognosis of high-grade serous ovarian carcinoma (HGSOC), however, their role in recurrent ovarian cancer is largely unknown. We therefore systematically investigated TIL densities and MHC class I and II (MHC1, 2) expression in the progression of HGSOC. EXPERIMENTAL DESIGN: CD3+, CD4+, CD8+ TILs and MHC1, 2 expression were evaluated by immunohistochemistry on tissue microarrays in 113 paired primary and recurrent HGSOC. TILs were quantified by image analysis. All patients had been included to the EU-funded OCTIPS FP7 project. RESULTS: CD3+, CD4+, CD8+ TILs and MHC1 and MHC2 expression showed significant correlations between primary and recurrent tumor levels (Spearman rho 0.427, 0.533, 0.361, 0.456, 0.526 respectively; P<.0001 each). Paired testing revealed higher CD4+ densities and MHC1 expression in recurrent tumors (Wilcoxon P=.034 and P=.018). There was also a shift towards higher CD3+ TILs levels in recurrent carcinomas when analyzing platinum-sensitive tumors only (Wilcoxon P=.026) and in pairs with recurrent tumor tissue from first relapse only (Wilcoxon P=.031). High MHC2 expression was the only parameter to be significantly linked to prolonged progression-free survival after first relapse (PFS2, log-rank P=.012). CONCLUSIONS: This is the first study that analyzed the development of TILs density and MHC expression in paired primary and recurrent HGSOC. The level of the antitumoral immune response in recurrent tumors was clearly dependent on the one in the primary tumor. Our data contribute to the understanding of temporal heterogeneity of HGSOC immune microenvironment and have implications for selection of samples for biomarker testing in the setting of immune-targeting therapeutics.
Issue Date: 18-Feb-2018
Date of Acceptance: 11-Jan-2018
URI: http://hdl.handle.net/10044/1/57519
DOI: https://dx.doi.org/10.1016/j.neo.2018.01.007
ISSN: 1522-8002
Publisher: Neoplasia
Start Page: 280
End Page: 288
Journal / Book Title: Neoplasia : An International Journal for Oncology Research
Volume: 20
Issue: 3
Copyright Statement: © 2018 The Authors. Published by Elsevier Inc. on behalf of Neoplasia Press, Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
Keywords: 1103 Clinical Sciences
Oncology & Carcinogenesis
Publication Status: Published
Conference Place: United States
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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