Targeting oxidative phosphorylation to increase the efficacy of radio- and immune- combination therapy.

Targeting oxidative phosphorylation to increase the efficacy of radio- and immune- combination therapy. Clin Cancer Res. 2021 Jan 08;: Authors: Boreel DF, Span PN, Heskamp S, Adema GJ, Bussink J Abstract As tumors grow, they upregulate glycolytic and oxidative metabolism to support their increased and altered energetic demands. These metabolic changes have major effects on the tumor microenvironment (TME). One of the properties leading to this aberrant metabolism is hypoxia, which occurs when tumors outgrow their, often chaotic, vasculature. This scarcity of oxygen is known to induce radioresistance, but can also have a disrupting effect on the anti-tumor immune response. Hypoxia inhibits immune effector cell function, while immune cells with a more suppressing phenotype become more active. Therefore, hypoxia strongly affects the efficacy of both radiotherapy and immunotherapy, as well as this therapy combination. Inhibition of oxidative phosphorylation (OXPHOS) is gaining interest for its ability to combat tumor hypoxia and there are strong indications that this results in a reactivation of the immune response. This strategy decreases oxygen consumption, leading to better oxygenation of hypoxic tumor areas and eventually an increase in immunogenic cell death induced by radio-immunotherapy combinations. Promising pre-clinical improvements in radio- and immunotherapy efficacy have been observed by the hypoxia reducing effect of OXPHOS...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research