Reactive oxygen species: Janus-faced molecules in the era of modern cancer therapy
Oxidative stress, that is, an unbalanced increase in reactive oxygen species (ROS), contributes to tumor-induced immune suppression and limits the efficacy of immunotherapy. Cancer cells have inherently increased ROS production, intracellularly through metabolic perturbations and extracellularly thr...
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2024-12-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/12/12/e009409.full |
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| author | Rolf Kiessling Elias S J Arnér Aine O’Reilly Wenchao Zhao Stina Wickström |
| author_facet | Rolf Kiessling Elias S J Arnér Aine O’Reilly Wenchao Zhao Stina Wickström |
| author_sort | Rolf Kiessling |
| collection | DOAJ |
| description | Oxidative stress, that is, an unbalanced increase in reactive oxygen species (ROS), contributes to tumor-induced immune suppression and limits the efficacy of immunotherapy. Cancer cells have inherently increased ROS production, intracellularly through metabolic perturbations and extracellularly through activation of NADPH oxidases, which promotes cancer progression. Further increased ROS production or impaired antioxidant systems, induced, for example, by chemotherapy or radiotherapy, can preferentially kill cancer cells over healthy cells. Inflammatory cell-derived ROS mediate immunosuppressive effects of myeloid-derived suppressor cells and activated granulocytes, hampering antitumor effector cells such as T cells and natural killer (NK) cells. Cancer therapies modulating ROS levels in tumors may thus have entirely different consequences when targeting cancer cells versus immune cells. Here we discuss the possibility of developing more efficient cancer therapies based on reduction-oxidation modulation, as either monotherapies or in combination with immunotherapy. Short-term, systemic administration of antioxidants or drugs blocking ROS production can boost the immune system and act in synergy with immunotherapy. However, prolonged use of antioxidants can instead enhance tumor progression. Alternatives to systemic antioxidant administration are under development where gene-modified or activated T cells and NK cells are shielded ex vivo against the harmful effects of ROS before the infusion to patients with cancer. |
| format | Article |
| id | doaj-art-e1494a1e9768405ebe1fce708f622634 |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-e1494a1e9768405ebe1fce708f6226342025-08-20T02:49:35ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262024-12-01121210.1136/jitc-2024-009409Reactive oxygen species: Janus-faced molecules in the era of modern cancer therapyRolf Kiessling0Elias S J Arnér1Aine O’Reilly2Wenchao Zhao3Stina Wickström4Department of Oncology-Pathology, Karolinska Institutet, Stockholm, SwedenDivision of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SwedenDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, SwedenDivision of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, SwedenDepartment of Oncology-Pathology, Karolinska Institutet, Stockholm, SwedenOxidative stress, that is, an unbalanced increase in reactive oxygen species (ROS), contributes to tumor-induced immune suppression and limits the efficacy of immunotherapy. Cancer cells have inherently increased ROS production, intracellularly through metabolic perturbations and extracellularly through activation of NADPH oxidases, which promotes cancer progression. Further increased ROS production or impaired antioxidant systems, induced, for example, by chemotherapy or radiotherapy, can preferentially kill cancer cells over healthy cells. Inflammatory cell-derived ROS mediate immunosuppressive effects of myeloid-derived suppressor cells and activated granulocytes, hampering antitumor effector cells such as T cells and natural killer (NK) cells. Cancer therapies modulating ROS levels in tumors may thus have entirely different consequences when targeting cancer cells versus immune cells. Here we discuss the possibility of developing more efficient cancer therapies based on reduction-oxidation modulation, as either monotherapies or in combination with immunotherapy. Short-term, systemic administration of antioxidants or drugs blocking ROS production can boost the immune system and act in synergy with immunotherapy. However, prolonged use of antioxidants can instead enhance tumor progression. Alternatives to systemic antioxidant administration are under development where gene-modified or activated T cells and NK cells are shielded ex vivo against the harmful effects of ROS before the infusion to patients with cancer.https://jitc.bmj.com/content/12/12/e009409.full |
| spellingShingle | Rolf Kiessling Elias S J Arnér Aine O’Reilly Wenchao Zhao Stina Wickström Reactive oxygen species: Janus-faced molecules in the era of modern cancer therapy Journal for ImmunoTherapy of Cancer |
| title | Reactive oxygen species: Janus-faced molecules in the era of modern cancer therapy |
| title_full | Reactive oxygen species: Janus-faced molecules in the era of modern cancer therapy |
| title_fullStr | Reactive oxygen species: Janus-faced molecules in the era of modern cancer therapy |
| title_full_unstemmed | Reactive oxygen species: Janus-faced molecules in the era of modern cancer therapy |
| title_short | Reactive oxygen species: Janus-faced molecules in the era of modern cancer therapy |
| title_sort | reactive oxygen species janus faced molecules in the era of modern cancer therapy |
| url | https://jitc.bmj.com/content/12/12/e009409.full |
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