The paper presents a comprehensive single-cell atlas of human double-negative T (DNT) cells across 23 different cancer types. By integrating data from over 2,300 samples, the authors identify 14 distinct DNT subsets that exhibit unique functional roles, such as cytotoxicity, antigen presentation, and immune regulation. A key finding highlights the T14_HLA-DR+ subset, which acts as an unconventional antigen-presenting cell and correlates with better patient responses to immunotherapy. The study also maps the differentiation trajectories of these cells, showing how they transition between active and exhausted states within the tumor microenvironment. Ultimately, this work demonstrates that DNT cells are a highly heterogeneous population with significant potential for improving cancer prognosis and therapeutic development.

References:

• Hao Q, Zhou T, Yan H, et al. A pan-cancer single cell landscape reveals heterogeneity and functional diversity of double-negative T cells[J]. Molecular Cancer, 2026.