The role of IL-1 in breast cancer progression and immune evasion
Purpose and aims
Despite recent advances in cancer treatment strategies, global data indicates that breast cancer still account for approximately 500,000 deaths among women annually. Every year, approximately 1500 women die from breast cancer in Sweden alone.
Chronic unresolving inflammation is believed to play a vital role in the pathogenesis of several types of cancers, including breast cancer. Interleukin-1 (IL-1) belongs to a large family of cytokines involved in innate immunity and inflammation. Among this large family members, the role of IL-1(alpha) and IL-1(beta) in autoimmunity and inflammation have been extensively studied.
However, the role of IL-1(alpha) and IL-1(beta) in the context of cancer is not fully understood as conflicting roles of these cytokines have been reported. The overall purpose of this research project is to investigate the functional consequences of targeting IL-1 in a breast tumor context.
This will be done in a collaboration between Cantargia AB and Lund University, Sweden, with the following specific goals;
(i) to determine the effect(s) of interleukin-1 receptor accessory protein (IL-1RAP) targeting on tumor progression, immune evasion and anti-tumor adaptive immune responses.
(ii) to determine the mechanism(s) of synergism between IL-1RAP targeting and chemotherapy (in vitro), and between IL-1RAP targeting and immunotherapy (in vivo).
(iii) to unravel possible alternative pathway(s) exploited by stromal cells during IL-1RAP inhibition.
Significance and scientific novelty
Although the role of IL-1 in innate immunity and inflammation have been extensively studied, our understanding of its role in breast cancer progression and immune evasion is limited. Triple negative breast cancer (TNBC) is the most aggressive form of breast cancer. Several studies have shown the effects of IL-1 signaling on certain subsets of stroma cells in TNBC but no study has been done on the functional consequence of targeting IL-1 in the context of TNBC and other breast cancers.