Dissecting the role of IL8 in cancer using a new IL8-humanized mouse model

IL8 is a pleiotropic chemokine with important roles in e.g. neutrophil chemotaxis, tumor growth, and angiogenesis. In addition, IL8 has also been associated to resistance against checkpoint inhibition.

Unsurprisingly, IL8 has emerged as an attractive cancer target for the pharmaceutical industry, and several clinical trials with IL8 blockade have been initiated.

However, the absence of IL8 in mice has prevented detailed in vivo investigations of the role of IL8 in cancer progression.

We have therefore generated a new improved IL8-humanized mouse model (Hum-IL8) with physiological expression of IL8 and its receptors CXCR1 and CXCR2.

We reasoned that the Hum-IL8 mouse model will serve as a powerful exploratory and predictive model, allowing us to uncover the precise roles of IL8 in tumor progression and resistance to immunotherapy.

Because Hum-IL8 mice have physiological expression of IL8, CXCR1 and CXCR2, they have several advantages compared to other mouse strains. First, they can be used to study the role of IL8 in human tumor growth in vivo. Second, they can be used to study the role of IL8 in immune responses in vivo. Third, they can be used for the testing of new IL8 blockers in vivo.

In this project we will use our newly generated Hum-IL8 mice to dissect the role of IL8 in cancer.

The aim of this project is thus to identify how IL8 drives tumor progression and resistance to immune therapy, thereby contributing to the development of new IL8-blockade based therapies.