Therapeutic Potential of IL-37 in Cervical Cancer: Suppression of Tumour Progression and Enhancement of CD47-Mediated Macrophage Phagocytosis.

Abstract

As a promising therapeutic approach, immunotherapy is being extensively investigated in cervical cancer. Although immunotherapy has been validated to improve progression-free survival and overall survival in clinical trials, the overall response rate for cervical cancer remains inadequate, necessitating further improvement. Interleukin (IL)-37, an emerging immunomodulator, exhibits antitumour potentials by inhibiting tumour progression and regulating tumour-associated macrophage recognition. We found a significant downregulation of IL-37 expression in cervical cancer, correlated with a poor prognosis. Moreover, the upregulation of IL-37 expression exhibited a suppressive effect on various tumorigenic processes, suppressing the proliferation, invasion, migration, apoptosis and angiogenesis of tumour cells. We also found that the upregulation of IL-37 suppressed cluster of differentiation 47 (CD47) expression in tumour cells via suppression of the signal transducer and activator of transcription 3 (STAT3) expression and phosphorylation, thereby enhancing macrophage recognition and phagocytosis to tumour cells, ultimately reducing immune evasion. Overall, our study highlighted the crucial role of IL-37 in antitumour efficacy and downregulating the expression of CD47 in tumour cells to reduce immune evasion, suggesting the potential of IL-37 as a prognostic biomarker in cervical cancer and offering innovative therapeutic strategies to improve cancer treatment outcomes.