Overcoming immunosuppression and pro-tumor inflammation in lung cancer with combined IL-1β and PD-1 inhibition

Abstract

Inflammation in the tumor microenvironment is a complicit and known carcinogenesis driver. Inhibition of IL-1β, one of the most abundant and influential cytokines in the tumor microenvironment, may enhance the efficacy of PD-1. In a post-hoc analysis of phase III cardiovascular CANTOS trial, canakinumab, a monoclonal anti-IL-1β antibody, significantly reduced lung cancer incidence. Immune checkpoint inhibition (ICI) is the standard of care in non-small-cell lung cancer. However, ICI efficacy is heavily impacted by programmed death ligand-1 (PD-L1) status. Most patients with non-small-cell lung cancer have low PD-L1 expression levels. Thus, combinational strategies are needed to improve ICI efficacy and expand its use. Here, we describe the preclinical and clinical evidence to support the combination of IL-1β and PD-1 under investigation in the CANOPY program. The perioperative use of canakinumab with or without PD-1 inhibition in the CANOPY-N trial is described as a potential chemotherapy-free immunotherapy strategy.

Keywords: IL-1 beta; immune checkpoint inhibitors; non-small-cell lung cancer; programmed cell death protein-1; proinflammatory cytokines; protumor inflammation.