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CDK8 is a checkpoint blocking NK cell anti-tumor functions in triple negative breast cancer

Abstract
Triple-negative breast cancer (TNBC) is an aggressive malignant disease accounting for approximately 15% of breast cancers - the most common type of cancer and the second most common cause of cancer-related deaths among women. The current standard-of-care treatment for patients is chemotherapy and surgery. Still, diagnosed patients have only a slim chance of survival and high rates of relapse. Thus, there is an intense interest in finding new therapeutic strategies and recent clinical trials combining chemotherapy with checkpoint inhibitors showed encouraging outcomes. When we studied the role of CDK8 - an oncogenic driver in several cancer types - in TNBC mouse models, we found a significantly impaired breast cancer progression and metastasis formation in the absence of CDK8. CDK8 did not alter the tumor cell proliferation in vitro and in vivo but this effect was strictly dependent on the presence of NK cells. In contrast, wild-type TNBC escaped recognition and elimination by the immune system. We now aim to further study the human relevance using cell lines and patient material. Thereby our study is at the center of current cancer research and will extend our knowledge for alternative treatment options for TNBC.
Lemma
CDK8 in TNBC cells blocks NK cell surveillance
Project leader
Gotthardt Dagmar
Duration
01.06.20-31.05.22
Programme
F├Ârderungsantrag - Wissenschaft und Forschung
Type of Research
Basic research
Vetmed Research Units
Institute of Pharmacology and Toxicology
Funded by
Stadt Wien, Rathausstra├če 14-16, 1082 Wien, Austria
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