AI Article Synopsis
- - MTH1 helps protect tumor cells from oxidative stress, which aids tumor growth and may also affect the immune response against the tumor.
- - The study tested the effects of a drug called karonudib, an MTH1 inhibitor, on tumor growth and immune cell activity in mouse models of mesothelioma.
- - Results showed that combining MTH1 inhibition with PD-L1 blockade is more effective in reducing tumor growth and improving immune responses than using either treatment alone, suggesting a potential new approach for treating mesothelioma.
Article Abstract
Background: MTH1 protects tumor cells and their supporting endothelium from lethal DNA damage triggered by oxidative stress in the tumor microenvironment, thus promoting tumor growth. The impact of MTH1 on the tumor-related immune compartment remains unknown. We hypothesized that MTH1 regulates immune fitness and therefore enhances the activity of currently used immunotherapeutic regimens.
Methods: Our hypotheses were validated in two syngeneic murine mesothelioma models using the clinically relevant MTH1 inhibitor, karonudib. We also examined the effect of combined MTH1 and PD-L1 blockade in mesothelioma progression, focusing on the main immune players.
Results: Karonudib administration enhances M1 macrophage polarization, stimulates CD8 expansion and promotes the activation of DC and T cells. Combined administration of PD-L1 and MTH1 inhibitors impairs mesothelioma tumor growth and mesothelioma-associated pleural effusion accumulation more effectively compared to each monotherapy.
Conclusions: Combined MTH1 and PD-L1 inhibition holds promise for the successful clinical management of mesothelioma.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605650 | PMC |
| http://dx.doi.org/10.3390/cancers15204962 | DOI Listing |
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