Targeting IL-33 in patients with cancer under immune checkpoint inhibitors for a better antitumor response and prevent thromboembolism?

• Published in: Journal for immunotherapy of cancer Vol. 13; no. 2; p. e010806
• Main Authors: Azzellino, Gianluca, Ginaldi, Lia, De Martinis, Massimo
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 06.02.2025; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Alarmin; Biomarkers; Cancer therapies; Cardiovascular disease; COVID-19; Cytokine; Cytokines; Diabetes; Editing; Heart attacks; Immune Checkpoint Inhibitor; Immunotherapy; Ischemia; Letter; Medical prognosis; Metabolism; Thromboembolism; Thrombosis; Visualization; Alarmin; Immune Checkpoint Inhibitor; Thrombosis; Cytokine
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1136/jitc-2024-010806

The authors demonstrate how by blocking both IL-33 and PD-L1 in the tumor microenvironment (TME) not only augmented T-cell responses but also modulated the TME toward an immunoinflammatory phenotype, suggesting that dual targeting IL-33 and PD-L1 therapeutic approaches hold promising potential for further clinical application.1 In patients with cancer, thromboembolism (TE) is a well-known complication during chemotherapy, as was recently demonstrated in a higher-than-expected incidence in subjects treated with immune checkpoint blockade (ICB).2 The decrease of IL-33 and the increase of sST2 was recently described as a new valuable biomarker for diagnosis and mortality prediction in patients with pulmonary TE. The action of IL-33 is exerted through the injury-related response of stromal/parenchymal cells, the protective and anti-inflammatory actions mediated by Treg cells, and the inflammatory actions of various recruited immune cell types, all of which are modulated by the dampening actions exerted by sST2. In human endothelial cells, IL-33 induces proinflammatory, proangiogenic and prothrombotic milieu.6 All these observations, contrary to what was stated at the beginning, lead us to hypothesize that the synergistic action highlighted by Nan et al may also obtain a protective action with respect to the increased thromboembolic risk detected in patients with cancer treated with ICBs.