Inflammation in cancer can both suppress tumor growth and promote tumorigenesis. In the tumor microenvironment (TME), inflammation characterized by inflammatory cells and other mediators including cytokines affects tumor development and progression and can have an impact on response to therapy. The inflammatory cytokine IL-1b is upregulated in several conditions including rheumatoid arthritis, chronic obstructive pulmonary disease, inflammatory bowel disease, as well as in different cancers including breast, gastric, pancreatic, and lung cancers. IL-1b contributes to the generation and accumulation of myeloid-derived suppressor cells (MDSCs). In the tumor microenvironment, MDSCs consist of a mixture of immature macrophages, immature dendritic cells and neutrophils, which can suppress the function of antitumor T cells. In addition, IL-1b is produced via activation of the inflammasome, which has been shown to promote the infiltration of MDSCs and tumor-associated macrophages (TAMs) into the TME. Downstream of IL-1b production are other inflammatory cytokines such as IL-6, IL-8, and IL-17, which can also suppress the immune system. Recently published data show that blocking IL-1b in patients without cancer can lead to a decrease in fatal cancer and more specifically lung cancer incidences and fatalities (Ridker et al., 2017). While the study was not designed to study the anticancer effects of canakinumab (Ilaris), this finding has led to increased interest in understanding the role of IL-1b and IL-1b blockade in cancer development and progression. Emerging data aim to elucidate the role of IL-1b blockade on tumor growth and progression, as well as characterize changes to tumor-infiltrating lymphocyte (TIL) populations and their function after treatment with an anti-IL-1b antibody.
Reference: Ridker PM et al. Effect of interleukin-1b inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomized, double-blind, placebo-controlled trial. Lancet 2017;390:1833-42.
Citation Format: Reshma Singh, Rohan Diwanji, Pushpa Jayaraman, Derek Chiang, Catherine Sabatos-Peyton, Glenn Dranoff. Anti IL-1b as a cancer immunotherapy [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr A76.