TGFβ inhibition prior to hypofractionated radiation enhances efficacy in preclinical models

Menée sur des modèles murins de cancer colorectal, cette étude montre que l'inhibition du facteur de croissance TGF bêta augmente l'efficacité d'une radiothérapie hypofractionnée

Résumé en anglais

The immune infiltrate in colorectal cancer has been correlated with outcome, such that individuals with higher infiltrations of T cells have increased survival independent of disease stage. For those patients with poor immune infiltrates, overall survival is severely limited. Since the colorectal cancer patients studied received conventional cancer therapies, these data could be interpreted to mean that the pre-treatment tumor environment increases the efficacy of treatments such as chemotherapy, surgical resection and radiation therapy. This study was designed to test the hypothesis that an improved immune environment in the tumor at the time of treatment will increase the efficacy of radiation therapy. We demonstrate that inhibition of TGFβ using the orally available small molecule inhibitor SM16 improved the immune environment of tumors in mice and significantly improved the efficacy of subsequent radiation therapy. This effect was not due to changes in radiosensitivity, epithelial to mesenchymal transition or changes in vascular function in the tumor; rather, this effect was dependent on adaptive immunity and resulted in long-term protective immunity in cured mice. These data demonstrate that immunotherapy is an option to improve the immune status of patients with poor tumor infiltrates and that pre-treatment improves the efficacy of radiation therapy.