The body’s response to cancer is complex, and boosting it requires strategy. White blood cells known as effector T cells are programmed to infiltrate tumors and control or kill tumor cells. But the microenvironment around a tumor can inhibit T cells, preventing an effective anti-tumor response. Although immune checkpoint blockade therapies can restore anti-tumor immunity, these treatments aren’t effective for everyone, and innovative approaches combining multiple pathways are needed. Now, researchers have identified a new potential target for anti-tumor therapy. Orphan nuclear receptor NR2F6 inhibits T cell activation. A recent study combined deletion of NR2F6 in T cells with conventional immune checkpoint therapy in mice. Researchers deleted NR2F6 in T cells using CRISPR/ Cas9 technology and reintroduced them into mice. NR2F6-deleted T cells in combination with checkpoint therapy allowed mice to survive injection of tumor cells, while checkpoint therapy alone did not. This suggests that targeting NR2F6 could boost anti-tumor immunity by sensitizing T cells to checkpoint therapy, making it valuable in the fight against cancer.