Thiopurine 6TG treatment increases tumor immunogenicity and response to immune checkpoint blockade

Immune-checkpoint inhibitors (ICI) are highly effective in reinvigorating T cells to attack cancer. Nevertheless, a large subset of patients fails to benefit from ICI, partly due to a lack of the cancer neoepitopes necessary to trigger an immune response. 6TG exposure increased the tumor mutational burden without affecting tumor cell proliferation and cell death. The author further validated that 6TG exposure improved tumor control in additional mouse models of melanoma. These findings have paved the way for a phase I/II clinical trial that explores whether treatment with thiopurines can increase the proportion of otherwise treatment-resistant cancer patients who may benefit from ICI therapy.