Cytokines such as IL-15, IL-2, IL-18, and IL-12 play a central role in activating cytotoxic immune cells, including T cells and natural killer (NK) cells, that can recognise and destroy cancer. In preclinical studies, these inflammatory cytokines are among the most potent anti-cancer agents when administered systemically. However, their clinical translation has been constrained by a narrow therapeutic window, as the doses required for efficacy frequently cause severe toxicities such as cytokine release syndrome, vascular leak, and immune-mediated organ damage.
This presentation will examine emerging strategies to safely harness cytokine activity by focusing it within the tumour microenvironment. These include small molecules that enhance cytokine receptor expression on tumour-infiltrating lymphocytes, nanoparticle-based delivery systems, oncolytic viruses engineered to express cytokines, and tumour-targeted biologics such as antibody–cytokine fusion proteins. Together, these approaches aim to amplify local immune activation while minimising systemic exposure.
In parallel, a growing class of NK cell–targeted modalities seeks to drive tumour inflammation and cytotoxicity directly. By selectively activating and expanding NK cells within tumours, these approaches can induce local cytokine release, tumour cell killing, antigen spread, and recruitment of adaptive immunity. NK-focused therapies therefore represent a complementary strategy to cytokine targeting, offering new opportunities to safely ignite anti-tumour inflammation and overcome resistance to existing immunotherapies.