Natural killer/T-cell lymphoma (NKTL) is an aggressive malignancy linked to Epstein–Barr virus infection and genomic hypermethylation. While anti–PD-1 therapies such as sintilimab have shown efficacy, only about one-third of patients achieve complete remission, and resistance almost always develops. Once relapse occurs, survival drops to just a few months, and no standard treatment exists.

To address this, an international team led by Jing Tan, PhD, and Huiqiang Huang, MD, at Sun Yat-sen University Cancer Center and Choon Kiat Ong, PhD, at Singapore’s National Cancer Centre, tested whether epigenetic therapy could overcome immune resistance. Their approach: pair PD-1 blockade with a DNMT inhibitor, either decitabine or azacitidine, to induce immune reactivation through a process known a

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