On Tuesday, Korea University announced a breakthrough in colorectal cancer treatment. A research team led by Professor Jeon Tae Hoon from the Department of Converging Biomedical Engineering has developed a novel strategy to boost immune responses against colorectal cancer by regulating tumor-associated macrophages.
Tumor-associated macrophages are immune cells that facilitate cancer growth, spread, and immune evasion. They are closely linked to poor patient outcomes and resistance to cancer therapies.
Traditionally, colorectal cancer treatment relied on surgery, radiation, and chemotherapy. Recently, immunotherapy has gained traction, stimulating the body’s immune cells to attack cancer. Immune checkpoint inhibitors, which counteract cancer’s ability to evade the immune system, have become a leading-edge treatment.
However, the efficacy of immune checkpoint inhibitors in colorectal cancer largely depends on the tumor’s MMR (mismatch repair) status. About 85% of colorectal cancers are of the MSS/pMMR type, which have fewer mutations and produce insufficient neoantigens for immune cell recognition. As a result, response rates to immune checkpoint inhibitors have remained disappointingly low, under 10%.
The research team analyzed tumor microenvironments from 62 colorectal cancer patients and 36 healthy individuals. They discovered an overexpression of the MAFB protein in tumor-associated macrophages, which impedes immunotherapy. Higher MAFB levels were associated with reduced responsiveness to pembrolizumab, a prominent immune checkpoint inhibitor.
MAFB was identified as a key transcriptional regulator that promotes the expression of critical factors in tumor-associated macrophages (ARG1, IL-4, IL-10). The team found that MAFB deficiency in macrophages transforms the tumor microenvironment from immunosuppressive to immunoactive, significantly enhancing the anti-tumor effects of immune checkpoint inhibitors in colorectal cancer.
These groundbreaking findings were published in the March issue of Translational Research, a top-tier journal in clinical pathology (ranked in the top 4.5% by Journal Citation Reports). This study was supported by the Mid-Career Research Program, funded by South Korea’s Ministry of Science and ICT and the National Research Foundation.