In this issue

SET facilitates immune escape of microsatellite stability colorectal cancer by inhibiting c-Myc degradationColorectal cancer (CRC) is a common type of cancer that affects many people worldwide.Most CRC cases are classified as microsatellite stable (MSS) CRC, which are particularly challenging to treat.A promising treatment called immune checkpoint blockade (ICB) therapy helps the immune system fight cancer, but MSS CRC doesn't respond well to it.This is because MSS CRC lacks key features, such as high mutation rates and active immune cells, that make it harder for the immune system to recognize the tumor as a threat.Researchers have identified a potential culprit behind this-the SET protein.SET is found in higher amounts in MSS CRC compared to another type of CRC that responds better to ICB therapy.SET increases the activity of mismatch repair proteins, which reduce mutation rates and prevent the immune system from recognizing the tumor.SET also suppresses the production of CCL5, a signaling molecule that normally attracts immune cells to the tumor, enabling the tumor to grow unchecked.Additionally, SET stabilizes c-Myc, a protein that promotes tumor growth and prevents immune cells from infiltrating it.By blocking SET, researchers made the tumors more visible to the immune system.As a result, more immune cells could infiltrate the tumor, making the cancer more susceptible to treatment.When SET inhibition was combined with ICB therapy, the immune response against MSS CRC was significantly improved.These findings suggest that targeting SET could be a new way to make MSS CRC more responsive to immunotherapy, improving treatment outcomes for patients with this difficult-to-treat cancer.