Tumors are complex ecosystems containing not just cancer cells, but a large variety of cell types, including immune cells. Moreover, tumors have a systemic influence: they can signal long distances... Show moreTumors are complex ecosystems containing not just cancer cells, but a large variety of cell types, including immune cells. Moreover, tumors have a systemic influence: they can signal long distances using soluble molecules and hijack non-neoplastic cells (such as immune cells) in distant organs for their own benefit, thus maximising their metastatic potential. The phenotype of immune cells in tumors and in systemic environments is therefore a key determinant of cancer progression and response to therapy.This thesis aims to understand what governs the tumor-immune ecosystem. We argue that cancer-intrinsic genetic aberrations have a dominant role in determining the tumor immune contexture, as well as systemic inflammatory activation. Understanding the intricate connection between the genetics of breast cancer and anti-tumor immune responses will help develop personalised immune intervention strategies for cancer, tailored to the genetic makeup of a patient’s tumor. Furthermore, we examine in detail the role of neutrophils in cancer-induced systemic inflammation, and how they influence the progression and spread of breast cancer. While tumors can be highly heterogeneous in nature, we show that neutrophils themselves also have a tremendous phenotypic diversity. Mapping this heterogeneity in neutrophil phenotypes may help to utilise these cells in cancer immunotherapy. Show less
Despite recent clinical advances, breast cancer still remains one of the main causes of cancer-related death in women. The majority of these deaths are caused by metastatic disease, which is... Show moreDespite recent clinical advances, breast cancer still remains one of the main causes of cancer-related death in women. The majority of these deaths are caused by metastatic disease, which is still poorly understood and incurable. Recent clinical and experimental studies have shown that the role of the immune system in cancer progression and therapy responsiveness is paradoxical. While some immune cells are able to attack and kill cancer cells, other populations counteract anti-tumor immune responses and promote cancer progression. To provide optimal treatment options for patients with disseminated cancer, we need to gain a better understanding of the delicate balance between pro- and anti-tumor immunity. This thesis describes the complex interactions between innate and adaptive immune cells that facilitate metastatic spread in a mouse model of spontaneous invasive breast cancer. Moreover, this thesis describes that the use of chemo-immunotherapy as a therapeutic strategy can enhance anti-tumor immunity to fight breast cancer. Show less
