Shanghai Children's Hospital Team Publishes in Science Immunology on Mechanism to Boost Solid Tumor Immunotherapy

The research team led by Professor Wang Feng at the Institute of Pediatric Infection, Immunity and Critical Care Medicine of Shanghai Children's Hospital and the Shanghai Institute of Immunology has published a paper in Science Immunology titled “PTMA safeguards mitochondrial integrity to sustain metabolic function and antitumor activity of CD8 T Cells.” The study found that prothymosin alpha (PTMA), a direct downstream target of the core transcription factor TCF1, binds to and stabilizes mitochondrial transcription factor A (TFAM), protecting the integrity of mitochondrial DNA and thereby sustaining oxidative phosphorylation metabolism and the durability of antitumor function in CD8 T cells. Analyzing single-cell transcriptomic data from patients with six types of human solid tumors who received immune checkpoint blockade therapy, the team found that PTMA is highly expressed in the treatment-responsive CD8 Tpex cell subset and correlates significantly with therapeutic efficacy. In mice with T cell-specific Ptma knockout, the effect of anti-PD-1 therapy was completely abolished, whereas PTMA overexpression significantly enhanced antitumor immune activity.

The findings reveal the TCF1-PTMA axis as a molecular bridge and offer a new strategy for reversing T cell exhaustion.