Deciphering tumor-promoting mechanisms mediated by neutrophils in vivo
Immunotherapies are revolutionizing cancer care, but are only effective in a minority of patients. Because current treatments typically target T lymphocytes, manipulating other cell types will create additional therapeutic opportunities. This research project aims to study neutrophils, because they can be abundant in the tumor environment, can modulate tumor outgrowth and response to treatments, and are candidate new therapeutic targets. However, tumor-associated neutrophils can be phenotypically and functionally heterogeneous, with only some of them promoting tumor growth. At present, we have a limited understanding of the complexity of neutrophils in tumors, and the mechanisms that control the functions of these cells. This is largely due to the inherent experimental limitations of neutrophil studies.  Here, we will use a new approach to test the hypotheses that so-called Conditionally-Immortalized Neutrophil Progenitors (CINP) can be: 1) used to produce unrestricted numbers of tumor-associated neutrophils in vivo, and 2) gene-edited to study neutrophils mechanistically during cancer progression. Addressing these questions bears scientific and therapeutic importance, as it will not only deepen our fundamental understanding of the mechanisms regulating neutrophil activities in cancer, but also indicate new molecular targets for therapy.   With this study, I will also create and share a publicly available database of all newly identified targets that will be investigated by us, other academic research groups, and industry. Besides, the project’s outputs will be communicated to the broader general public. Altogether, the training and input I will receive during the Marie Curie Individual Fellowship will prepare my transition from post-doc to independent researcher in an excellent scientific environment in Europe.