Immune Suppression Through Intron Retention by Oncogenic SRSF10

Most researchers dismiss introns as irrelevant blocks of DNA information. What if they are actually an integral part of cancer metastases?

Metastatic colorectal cancer (mCRC) is a major cause of cancer deaths worldwide. One of the main challenges in treating mCRC is that in most cases the cancer escapes the immune system, preventing attack on the tumor. Dr. Pitroda’s lab recently discovered a new way that mCRC blocks the immune system. Specifically, mCRC impairs the molecular machinery that signals problems in a cell to the immune system. During the expression of our genes into proteins, irrelevant blocks of information called introns are deleted from the instructions for making proteins. Dr. Pitroda has found that mCRC
blocks the creation of immune signals by preventing the deletion of these introns, leading to instructions that amount to gibberish. No previous studies have shown that such intron retention plays a role in immune resistance. Importantly, Dr. Pitroda has implicated a protein, called SRSF10, in mediating this intron retention. His research suggests that by targeting this protein for intron retention, we could enhance the immune system’s ability to fight the cancer and improve the effectiveness of
immunotherapies. Using his Fletcher Scholar’s Award, Dr. Pitroda will test whether attacking mCRC activates SRSF10, which in turn blocks the deletion of introns, disabling immune signaling and helping tumor cells evade the immune response. This would be the first study to show how a protein factor like SRSF10 contributes to immune suppression through intron retention. By targeting these immune resistance mechanisms, Dr. Pitroda aims to find a cure for patients with mCRC with an approach that could revolutionize cancer treatment and would focus on as patients with metastatic cancer, mostly considered incurable despite current advances in medical treatments.