Absence of PD-L1 on tumor cells is associated with reduced MHC I expression and PD-L1 expression increases in recurrent serous ovarian cancer
- Author(s)
- Stefanie Aust, Sophie Felix, Katharina Auer, Anna Bachmayr-Heyda, Lukas Kenner, Sabine Dekan, Samuel M. Meier, Christopher Gerner, Christoph Grimm, Dietmar Pils
- 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.
- Organisation(s)
- Department of Analytical Chemistry, Mass Spectrometry Centre
- External organisation(s)
- Medizinische Universität Wien
- Journal
- Scientific Reports
- Volume
- 7
- No. of pages
- 12
- ISSN
- 2045-2322
- DOI
- https://doi.org/10.1038/srep42929
- Publication date
- 03-2017
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 301904 Cancer research
- Keywords
- ASJC Scopus subject areas
- General
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/b11bf1fe-2638-437e-8057-9f33a306bd7f