Oncotarget

Research Papers:

Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer

Katharina Auer, Anna Bachmayr-Heyda, Nyamdelger Sukhbaatar, Stefanie Aust, Klaus G. Schmetterer, Samuel M. Meier, Christopher Gerner, Christoph Grimm, Reinhard Horvat and Dietmar Pils _

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Oncotarget. 2016; 7:61336-61354. https://doi.org/10.18632/oncotarget.11038

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Abstract

Katharina Auer1, Anna Bachmayr-Heyda1, Nyamdelger Sukhbaatar1, Stefanie Aust1, Klaus G. Schmetterer2, Samuel M. Meier3, Christopher Gerner3, Christoph Grimm1, Reinhard Horvat4, Dietmar Pils1

1Department of Obstetrics and Gynecology, Medical University of Vienna and Comprehensive Cancer Center, Vienna, Austria

2Department for Laboratory Medicine, Medical University of Vienna, Vienna, Austria

3Department of Analytical Chemistry, University of Vienna, Vienna, Austria

4Department of Pathology, Medical University of Vienna, Vienna, Austria

Correspondence to:

Dietmar Pils, email: [email protected]

Keywords: epithelial ovarian cancer, peritoneal tumor spread, flow cytometry, PD-1, next generation sequencing

Received: May 05, 2016     Accepted: July 14, 2016     Published: August 03, 2016

ABSTRACT

The immune system plays a critical role in cancer progression and overall survival. Still, it is unclear if differences in the immune response are associated with different patterns of tumor spread apparent in high grade serous ovarian cancer patients and previously described by us. In this study we aimed to assess the role of the immune system in miliary (widespread, millet-sized lesions) and non-miliary (bigger, exophytically growing implants) tumor spread. To achieve this we comprehensively analyzed tumor tissues, blood, and ascites from 41 patients using immunofluorescence, flow cytometry, RNA sequencing, multiplexed immunoassays, and immunohistochemistry. Results showed that inflammation markers were systemically higher in miliary. In contrast, in non-miliary lymphocyte and monocyte/macrophage infiltration into the ascites was higher as well as the levels of PD-1 expression in tumor associated cytotoxic T-lymphocytes and PD-L1 expression in tumor cells. Furthermore, in ascites of miliary patients more epithelial tumor cells were present compared to non-miliary, possibly due to the active down-regulation of anti-tumor responses by B-cells and regulatory T-cells. Summarizing, adaptive immune responses prevailed in patients with non-miliary spread, whereas in patients with miliary spread a higher involvement of the innate immune system was apparent while adaptive responses were counteracted by immune suppressive cells and factors.


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