title: Absence of PD-L1 on tumor cells is associated with reduced MHC I expression and PD-L1 expression increases in recurrent serous ovarian cancer.
abstract: Immune-evasion and immune checkpoints are promising new therapeutic targets for several cancer entities. In ovarian cancer, the clinical role of programmed cell death receptor ligand 1 (PD-L1) expression as mechanism to escape immune recognition has not been clarified yet. We analyzed PD-L1 expression of primary ovarian and peritoneal tumor tissues together with several other parameters (whole transcriptomes of isolated tumor cells, local and systemic immune cells, systemic cytokines and metabolites) and compared PD-L1 expression between primary tumor and tumor recurrences. All expressed major histocompatibility complex (MHC) I genes were negatively correlated to PD-L1 abundances on tumor tissues, indicating two mutually exclusive immune-evasion mechanisms in ovarian cancer: either down-regulation of T-cell mediated immunity by PD-L1 expression or silencing of self-antigen presentation by down-regulation of the MHC I complex. In our cohort and in most of published evidences in ovarian cancer, low PD-L1 expression is associated with unfavorable outcome. Differences in immune cell populations, cytokines, and metabolites strengthen this picture and suggest the existence of concurrent pathways for progression of this disease. Furthermore, recurrences showed significantly increased PD-L1 expression compared to the primary tumors, supporting trials of checkpoint inhibition in the recurrent setting.
authors.affiliation: Dept. of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Aust
authors.affiliation: Dept. of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria.
authors.forename: Sophie
authors.initials: S
authors.lastname: Felix
authors.affiliation: Dept. of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Auer
authors.affiliation: Dept. of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria.
authors.forename: Anna
authors.initials: A
authors.lastname: Bachmayr-Heyda
authors.affiliation: Dept. of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Lukas
authors.initials: L
authors.lastname: Kenner
authors.affiliation: Dept. of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Sabine
authors.initials: S
authors.lastname: Dekan
authors.affiliation: Dept. of Analytical Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Meier
authors.affiliation: Dept. of Analytical Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Christopher
authors.initials: C
authors.lastname: Gerner
authors.affiliation: Dept. of Obstetrics and Gynecology, Comprehensive Cancer Center (CCC), Medical University of Vienna, Vienna, Austria.
authors.forename: Christoph
authors.initials: C
authors.lastname: Grimm
authors.affiliation: Section for Clinical Biometrics, Center for Medical Statistics, Informatics, and Intelligent Systems (CeMSIIS), Medical University of Vienna, Vienna, Austria.|Dept. of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pils
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006680:HLA Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010051:Ovarian Neoplasms / Q000401:mortality / Q000473:pathology*; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood
chemical_list: D018925:Chemokines; D016207:Cytokines; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D061026:Programmed Cell Death 1 Receptor; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human