Functional Characterization of Neutrophil type I IFN and TGFβ Signaling in Cancer

• Applicant: Professorin Dr. Jadwiga Jablonska-Koch
• Subject Area: Immunology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 443221573

Neutrophils in cancer have the potential to fight cancer, and limit tumor growth and metastatic progression. However, neutrophil beneficial functions are often blocked by TGFβ. Furthermore, TGFβ can propagate the expansion of tumor-promoting neutrophil subsets and promote neutrophil mediated suppression of adaptive immunity. On the other hand, IFNs are known to support anti-tumor capabilities of neutrophils. The proposed research aims at gaining in depth understanding of the mechanism through which both pathways regulate distinct neutrophil functions. To this end, we will utilize novel genetic tools to perturb both canonical and non-canonical TGFβ signaling, or STAT3-mediated IFN signaling in a neutrophil specific manner. We will then test how perturbing these signaling pathways affect the functional response to TGFβ or IFN, and ultimately, how perturbing these pathways affects tumor growth and metastatic progression. In summary, the successful completion of the proposed experiments will enhance our understanding of the complex role neutrophils play in cancer. Moreover, the proposed study will highlight signaling pathways that may be targeted therapeutically and benefit cancer patients. Targeting these pathways will be pathway specific and therefore expected to be safer than systemic TGFβ blockade or IFN therapy, and may serve as a platform for the development of novel neutrophil mediated anti-cancer immunotherapy.

• DFG Programme: Research Grants
• International Connection: Israel
• International Co-Applicant: Professor Dr. Zvika Granot