Karin de Visser Group
Inflammation and cancer
Metastasis formation and unresponsiveness to conventional therapies are the challenges in cancer therapy that most urgently need solutions. The overall goal of our research is to understand by which mechanisms the immune system impacts on breast cancer metastasis and response to conventional anti-cancer therapies. To mechanistically elucidate how immune cells affect metastasis, we have established a novel pre-clinical mouse model of spontaneous breast cancer metastasis that mimics the clinical course of metastatic disease in humans. We have recently discovered that breast tumors maximize their chance of metastasizing by evoking a systemic inflammatory cascade involving IL17-producing γδ T cells and immunosuppressive neutrophils. The goal of our current studies is to mechanistically dissect how the genetic make-up of cancers dictates pro-metastatic systemic inflammation, and to elucidate the pro-metastatic functions of tumor-induced neutrophils.
In parallel, using in vivo tumor models that faithfully recapitulate human breast tumorigenesis, we dissect the impact of the inflammatory tumor microenvironment on the anti-cancer efficacy of chemo- and immunotherapy. We found that macrophages counteract the anti-cancer efficacy of chemotherapy in a drug dependent fashion. We discovered that macrophage inhibition through CSF-1R blockade together with cisplatin treatment evoked a compensatory neutrophil response limiting the synergistic anti-cancer effect of this combination. The goal of our current projects is to understand the mechanisms by which myeloid cells counteract the efficacy of anti-cancer therapies, and to dissect the deleterious feedback mechanisms within the immune system upon treatment with immunomodulatory therapies. Ultimately, through mechanistic understanding of the crosstalk between the immune system and cancer, we aim to contribute to the design of novel immunomodulatory strategies to fight metastatic breast cancer and to increase the efficacy of conventional anti-cancer therapies.