Innovative Immunotherapy Combination Effectively Targets Colorectal Liver Metastases

Advanced colorectal cancer frequently leads to liver metastases, posing significant treatment challenges. Despite improvements in surgical interventions, many patients experience tumor recurrence in the liver, highlighting the urgent need for more effective therapies.

Recent research from the University of California, San Francisco (UCSF) has unveiled promising developments in immunotherapy approaches for metastatic colorectal cancer. A groundbreaking study published in Science Advances demonstrates that a novel combination of immunotherapies can reprogram the immune environment within liver metastases, often resulting in complete tumor elimination in preclinical models.

The key to this discovery lies in targeting specific immune signals to enhance the body's natural defenses against cancer. Researchers focused on overexpressing the cytokine LIGHT (TNFSF14), which is known to stimulate immune activity. In combination with immune checkpoint blockade—specifically anti-CTLA-4 therapy—this strategy effectively reshaped the tumor microenvironment, overcoming the resistance typically seen in microsatellite stable (MSS) colon cancers, which constitute over 95% of colorectal cases.

Dr. Ajay V. Maker, the senior author of the study and a leading expert in surgical oncology at UCSF, explained that the combination therapy activates T cells and recruits immune cells capable of attacking the tumor. In models of liver metastases, the pairing of LIGHT overexpression with anti-CTLA-4 antibody led to robust control and destruction of tumors.

This approach addresses the known resistance of colorectal liver metastases to conventional immunotherapies. By strategically delivering these therapies directly into the liver and metastatic sites, researchers aim to translate these findings into clinical practice. The ultimate goal is to develop new, effective immunotherapy protocols that can provide long-lasting control or eradication of metastatic tumors, significantly improving patient outcomes.

The findings mark a major step forward in understanding how to manipulate the immune microenvironment in metastatic colorectal cancer. Future research is expected to focus on optimizing delivery methods and assessing safety and efficacy in clinical trials.

For more details, see the study: Bridget P. Keenan et al., "Combination LIGHT overexpression and checkpoint blockade disrupts the tumor immune environment impacting colorectal liver metastases," Science Advances, 2025. Link to study.

Source: https://medicalxpress.com/news/2025-10-immunotherapy-combination-destroys-colorectal-liver.html