New Insights into Why Immunotherapy Fails and How to Overcome Resistance in Cancer Treatment

Recent research published by the University of Birmingham and the University of Turku has uncovered crucial mechanisms behind the failure of immunotherapy in many cancer patients. Using advanced techniques, scientists identified a secreted form of the protein Clever-1, known as sClever-1, which plays a key role in immune suppression during cancer progression. Elevated levels of sClever-1 in the bloodstream are associated with resistance to anti-PD-1 therapies, a common class of cancer immunotherapies.

The study revealed that the investigational drug bexmarilimab, an anti-Clever-1 antibody, effectively inhibits the release of sClever-1, thereby potentially restoring immune system activity against tumors. This discovery provides a promising avenue for predicting which patients may not benefit from standard immunotherapy and highlights the potential of combination treatments that target sClever-1 to improve outcomes.

Lead researcher Professor Shishir Shetty from the University of Birmingham explained that high blood levels of sClever-1 could serve as a biomarker for immunotherapy resistance, allowing clinicians to tailor treatments more effectively. Similarly, Dr. Maija Hollmén from the University of Turku emphasized that reducing sClever-1 release may reprogram immune cells to fight cancer more efficiently.

The research, presented at the 19th International Congress of Immunology, analyzed plasma samples from 138 breast cancer patients, 193 individuals with advanced solid tumors, and 21 healthy donors. The findings indicate that inflammatory signals in the tumor microenvironment prompt macrophages to release sClever-1, which then impairs T cell responses by binding directly to these immune cells. This process effectively paralyzes the immune system’s ability to attack cancer cells.

Overall, these insights pave the way for new therapeutic approaches that can overcome immune evasion in cancer, potentially making immunotherapy accessible to more patients and improving long-term survival rates.

Source: https://medicalxpress.com/news/2025-09-immunotherapy-failure-patients-cancer.html