Targeting interleukin-1β and inflammation in lung cancer

Inflammation is a process that protects organs against various potentially harmful stimuli and enables repair. Dysregulated inflammation, however, damages tissues and leads to disease, including cancer. Cancer-related inflammation is characterized by cytokine production, leukocyte infiltration, angiogenesis, and tissue remodeling-all critical processes in modulating the tumor microenvironment (TME). The TME is known to play a key role in tumor progression, and targeting its immune component to achieve a better anti-tumor response is the basis of immunotherapy. Despite the critical role cytokines play in the TME and tumor progression, there is currently only one therapy approved by the FDA that directly involves cytokine signaling: human recombinant interleukin-2 protein, aldesleukin. The recent Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) trial evaluated the use of anti-interleukin-1β therapy in atherosclerotic disease; however, it also revealed interleukin-1β (IL-1β) blockade with canakinumab led to a significantly lower incidence of lung cancer. This has opened a promising new avenue for lung cancer therapy, and strategies using anti-IL-1β therapy alone or in combination with chemotherapy and/or immune checkpoint blockade are currently being evaluated in several clinical trials.