NOX2 as a biomarker of radiotherapy efficiency in cancer patients
US11603568B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Sep 19, 2017 |
| Grant date | Mar 14, 2023 |
| Priority date | — |
| Expiry date | Jan 5, 2038 |
Classification
- Technology area (CPC G)Physics
- CPC primaryG01N2800/52
- WIPO fieldMeasurement
- WIPO sectorInstruments
Abstract
Although tumor-associated macrophages have been extensively studied in the control of response to radiotherapy, the molecular mechanisms involved in the ionizing radiation-mediated activation of macrophages remain elusive. Here the present inventors show that ionizing radiation induces the expression of interferon-regulatory factor 5 (IRF5) promoting thus macrophage activation toward a pro-inflammatory phenotype. They reveal that the activation of the Ataxia telangiectasia mutated (ATM) kinase is required for ionizing radiation-elicited macrophage activation, but also for macrophage reprogramming after treatments with γ-interferon, lipopolysaccharide or chemotherapeutic agent (such as cis-platin), underscoring the fact that the kinase ATM plays a central role during macrophage phenotypic switching toward a proinflammatory phenotype. They further demonstrate that NADPH oxidase 2 (NOX2)-dependent ROS production is upstream to ATM activation and is essential during this process. They also report that hypoxic conditions and the inhibition of any component of this signaling pathway (NOX2, ROS and ATM) impairs pro-inflammatory activation of macrophages and predicts a poor tumor response …
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.