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Targeting immune checkpoint therapy: the role of manganese in tumour immunotherapy

3 Nov 2025
Targeting immune checkpoint therapy: the role of manganese in tumour immunotherapy

Cancer immunotherapy has emerged as a promising complement to traditional treatments such as radiotherapy and chemotherapy.

Although conventional therapies remain central to cancer management, the potential of immunotherapy is increasingly recognised.

Immune checkpoint therapy, a key strategy in tumour immunotherapy, has demonstrated significant efficacy against solid tumours.

However, its clinical application is hindered by its limited response rate, necessitating efforts to optimise its effectiveness.

Recent studies have highlighted the pivotal role of the cyclic GMP-AMP synthase (cGAS) - stimulator of interferon gene (STING) pathway in immune checkpoint therapy.

Manganese (Mn), an essential trace element, regulates the activity of CD8+ T and NK cells by modulating the cGAS-STING pathway.

Furthermore, the combination of Mn with anti-programmed cell death protein 1 therapy has demonstrated promising anti-tumour effects.

Mn also influences immunogenic cell death (ICD), further augmenting its potential as an adjunct to tumour immunotherapy.

Despite a growing body of research on the role of Mn in modulating the cGAS-STING pathway and inducing ICD, comprehensive reviews that synthesise these findings and explore the potential of Mn in enhancing immune checkpoint therapy remain scarce.

This review aimed to fill this gap by examining the immune mechanisms by which Mn enhances immune checkpoint therapy and its overall impact on tumour immunotherapy.

Source: Chinese Medical Journals Publishing House Co., Ltd.