Harnessing cytokines and chemokines for cancer therapy

A variety of cytokines have diverse antitumour and/or pro-tumour activities and, accordingly, alterations in cytokine networks contribute to cancer development and progression. Therefore, cytokines and their receptors have long been investigated as therapeutic agents or targets in oncology, although with mostly disappointing results. Herein, Propper and Balkwill discuss the lessons learnt from initial clinical trials of monotherapy approaches as well as subsequent strategies to better leverage cytokines and cytokine antagonists in the treatment of solid tumours. During the past 40 years, cytokines and cytokine receptors have been extensively investigated as either cancer targets or cancer treatments. A strong preclinical rationale supports therapeutic strategies to enhance the growth inhibitory and immunostimulatory effects of interferons and interleukins, including IL-2, IL-7, IL-12 and IL-15, or to inhibit the inflammatory and tumour-promoting actions of cytokines such as TNF, IL-1 beta and IL-6. This rationale is underscored by the discovery of altered and dysregulated cytokine expression in all human cancers. These findings prompted clinical trials of several cytokines or cytokine antagonists, revealing relevant biological activity but limited therapeutic efficacy. However, most trials involved patients with advanced-stage disease, which might not be the optimal setting for cytokine-based therapy. The advent of more effective immunotherapies and an increased understanding of the tumour microenvironment have presented new approaches to harnessing cytokine networks in the treatment of cancer, which include using cytokine-based therapies to enhance the activity or alleviate the immune-related toxicities of other treatments as well as to target early stage cancers. Many challenges remain, especially concerning delivery methods, context dependencies, and the pleiotropic, redundant and often conflicting actions of many cytokines. Herein, we discuss the lessons learnt from the initial trials of single-agent cytokine-based therapies and subsequent efforts to better exploit such agents for the treatment of solid tumours.

Automated summary

Cytokines play a crucial role in cancer development and progression. While cytokines have been studied for their therapeutic potential in oncology, clinical trials have shown limited efficacy. However, the advent of immunotherapies and a better understanding of the tumor microenvironment have opened up new possibilities for harnessing cytokine networks in cancer treatment.