Breakthrough in Cancer Immunotherapy: Targeting the Molecular Brake to Enhance T Cell Response

Scientists at Harvard Medical School have uncovered a new molecular mechanism that could significantly improve cancer immunotherapy. They identified a protein called STUB1 that acts as a molecular brake on CD8+ T cells, the immune cells responsible for attacking tumors. This protein interferes with immune-signaling receptors, particularly one for the cytokine IL-27, which is crucial for mounting an effective anti-tumor response.

Using CRISPR gene-editing technology, researchers screened nearly 900 genes and discovered that deleting STUB1 in T cells dramatically increased their ability to target and destroy cancer cells. Mice with STUB1-deficient T cells showed slower tumor growth and longer survival, indicating the potential for therapeutic benefits.

Further investigations revealed that STUB1 interacts with another protein called CHIC2, leading to the removal of vital cytokine receptors from the T cell surface. This downregulates the T cells’ responsiveness to immune signals. Blocking this interaction could enhance immune responses and offer a new pathway for cancer treatments.

Although much of the research was performed in mice, experiments on human T cells showed similar results, suggesting that inhibiting STUB1 might boost cytokine signaling in humans as well. Notably, IL-27 has been associated with improved responses to immunotherapy in cancer patients, making STUB1 an attractive target.

The potential to develop drugs that inhibit STUB1 or engineer T cells without it presents exciting avenues for therapy. Such strategies could amplify the body's natural immune response while simultaneously making tumors more vulnerable to attack. Moreover, blocking STUB1 could complement existing treatments or serve as a monotherapy.

These findings fill critical gaps in understanding how T cells are primed to fight cancer and may lead to more effective and targeted immunotherapies. However, further research is needed to assess safety and efficacy in humans.

Source: [https://medicalxpress.com/news/2025-08-molecular-cells-supercharge-cancer-immunotherapy.html]