Project Details
Projekt
Redox metabolism as regulator of MDSCs-BCSC interactions in TNBC
Subject Area
Pediatric and Adolescent Medicine
Gynaecology and Obstetrics
Gynaecology and Obstetrics
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 549780759
Breast cancer is the most frequently diagnosed cancer in women and one of the leading causes of cancer death. In 2020 the WHO documented 2.3 million women diagnosed with breast cancer and 685,000 deaths globally. Triple-negative breast cancer (TNBC), the most aggressive subtype, is difficult to treat and has a poor prognosis especially in case of metastatic progression. Therefore, a reliable and effective strategy is urgently needed. The tumor immune microenvironment is decisive for tumor progression and metastasis. Especially myeloid derived suppressor cells (MDSCs) arise in the tumor environment. In addition to their immune-suppressive activity, MDSC are involved in tumor metastasis by participating in the formation of pre-metastatic niches, promoting angiogenesis and tumor cell invasion. Cancer stem cells (CSCs) are a small subset of cancer cells within the tumor. Due to their ability to self-renew and produce differentiated progeny they are suggested to drive tumor progression as well. There is accumulating evidence of a vicious cycle of CSCs recruiting MDSCs and MDSCs preserving CSCs’ existence. Our preliminary data show that oxidative stress mediated NRF2 signaling critically regulates MDSCs and drives cancer progression. While the direct immunosuppressive function of MDSCs is well documented, the mechanism of interaction with CSCs is less clear. We will analyze the interaction of MDSCs with breast CSCs (BCSCs) with a focus on oxidative stress induced NRF2 signaling. We will therefore directly measure NRF2 activation in MDSCs in different stages of cancer and will then make use of a complex in vitro setting to uncover mechanisms of MDSC-BCSC interactions and subsequent effects on tumor progression and tumor metastasis and will finally analyze how Nrf2 signaling in MDSCs impacts breast cancer development in vivo. By doing so this approach will provide substantial insights into MDSC-BCSC interactions in TNBC and provide novel therapeutic options.
DFG Programme
Research Grants
