Role of the immune system in the peritoneal tumor spread of high grade serous ovarian cancer.
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.
Department of Obstetrics and Gynecology, Medical University of Vienna and Comprehensive Cancer Center, Vienna, Austria.
Katharina
K
Auer
Department of Obstetrics and Gynecology, Medical University of Vienna and Comprehensive Cancer Center, Vienna, Austria.
Anna
A
Bachmayr-Heyda
Department of Obstetrics and Gynecology, Medical University of Vienna and Comprehensive Cancer Center, Vienna, Austria.
Nyamdelger
N
Sukhbaatar
Department of Obstetrics and Gynecology, Medical University of Vienna and Comprehensive Cancer Center, Vienna, Austria.
Stefanie
S
Aust
Department for Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Klaus G
KG
Schmetterer
Department of Analytical Chemistry, University of Vienna, Vienna, Austria.
Samuel M
SM
Meier
Department of Analytical Chemistry, University of Vienna, Vienna, Austria.
Christopher
C
Gerner
Department of Obstetrics and Gynecology, Medical University of Vienna and Comprehensive Cancer Center, Vienna, Austria.
Christoph
C
Grimm
Department of Pathology, Medical University of Vienna, Vienna, Austria.
Reinhard
R
Horvat
Department of Obstetrics and Gynecology, Medical University of Vienna and Comprehensive Cancer Center, Vienna, Austria.
Dietmar
D
Pils
D056704:Adaptive Immunity; D000951:Antigens, Neoplasm / Q000276:immunology; D001201:Ascites; D001402:B-Lymphocytes / Q000378:metabolism; D002469:Cell Separation; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007113:Immunity, Innate; D007118:Immunoassay; D007150:Immunohistochemistry; D007249:Inflammation; D008264:Macrophages / Q000378:metabolism; D055432:Metabolomics; D009000:Monocytes / Q000166:cytology; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000556:secondary; D017423:Sequence Analysis, RNA; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D016896:Treatment Outcome; D059016:Tumor Microenvironment
D000951:Antigens, Neoplasm
PD-1; epithelial ovarian cancer; flow cytometry; next generation sequencing; peritoneal tumor spread
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