Cytokine-based immunotherapy in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, characterized by a highly fibrotic and immunosuppressive tumor microenvironment that poses significant challenges to conventional therapies. In recent years, immunotherapy has emerged as a promising treatment approach for PDAC, yielding notable clinical results. While checkpoint blockade inhibitors and chimeric antigen receptor (CAR) T-cell therapies are the most well-known immunotherapies widely tested in clinical trials, cytokine therapy has also demonstrated effectiveness against PDAC in both preclinical and clinical settings, often in combination with other treatments rather than as monotherapy. This chapter explores the emerging potential of cytokine-based immunotherapies, focusing on strategies such as cytokine modulation, adoptive cell transfer therapies (including CAR-T and cytokine-induced killer cells), and combination treatments. We review preclinical approaches involving cytokine engineering and modulation of cell signaling, as well as various clinical studies specifically targeting pancreatic cancer. Although past and ongoing clinical trials highlight the promise of cytokine-related therapeutics as innovative treatment avenues, the full potential of this rapidly evolving field remains to be fully realized.