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The role of IL1 in tumor progression and immune evasion

Principle investigator Karin Leandersson

 

The area of this project is human tumor immunology, with a focus on innate immune cells and the tumor microenvironment. We will study the role of IL1α/β and innate immune cells in a tumor context, and their possible effects on tumor eradication, immune evasion and tumor progression. This will be done by using therapeutic targeting of IL1α/β using blocking strategies currently undergoing clinical development in cancer.

Interleukin-1 (IL1) is a central cytokine of the innate immune system. The IL-1 receptor (IL1R1) is part of the innate family of pattern recognition receptors (PRRs) sharing similarities with the Toll like receptor family (Toll-IL1-Receptor (TIR) domains) and being a crucial inducer of innate inflammation. IL1R1 binds IL1 and interacts with IL1 Receptor Accessory Protein (IL1RAP) to mediate signaling. There are two IL1 proteins; IL1α expressed by most cell types as a damage associated molecular pattern (DAMP), and ILβ being secreted by innate immune cells as a pro-inflammatory cytokine, tightly linked to the inflammasome. Tumors and cells of the tumor microenvironment may also express IL1α and IL1β, thus affecting tumor progression, metastasis, immune evasion and even cachexia. Due to the extremely potent and regulatory mechanisms of IL1α/β, more knowledge is greatly needed to understand their context in cancer and tumor immunology and the consequences of targeting them in different cancer indications.

The aim with this project is to investigate the functional consequences of targeting IL1 in a tumor context, and on subsequent effects this might have on tumor progression, immune evasion and anti-tumor adaptive immune responses. The consequence of intervening with the IL1 system using specific IL1α/β blocking strategies will be performed. Clinical data indicate that IL1 inhibition reduces tumor incidence in non-small cell lung cancer (NSCLC) and leads to increased response to treatment in NSCLC and pancreatic ductal adenocarcinoma (PDAC) when combined with chemotherapy. The mechanism behind this is however not completely clear and this project will be relevant to understand and further develop the concept of IL1 blockade in cancer. The project will be performed at Cancer Immunology (Lund University) in close collaboration with Cantargia AB. Cantargia develops IL1RAP-targeting antibodies for treatment of cancer and inflammation and has reached clinical phase II in non-small cell lung cancer and pancreatic cancer.

Key requirements:

·      PhD in Immunology, Tumor immunology or Tumor biology.

·      Strong publication record.

·      Experience in primary cell work, cell sorting, multiparameter flow cytometry, and immunological assays.

 

Advantageous skills:

·      Knowledge in human (as compared to mouse) immunology, but the level of knowledge is always more important than species.

·      Knowledge in the area of immune oncology and immunotherapy.

·      Experience in in vitro assays associated with human immunology (IF, IHC, flow cytometry and cell sorting, ELISA, CyTOF, gene expression profiling)

·      Experience in Bioinformatics and statistics programs.

·      Able to communicate effectively across language, cultural, or other barriers.

      ·      Ability to manage projects independently.

 

Partners: Cancer immunology (Malmö, Lund University) and Cantargia AB (Lund).

Homepage: Karin Leandersson; Cantagaria