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SOX17 enables immune evasion of early colorectal adenomas and cancers
Being able to treat colorectal cancer (CRC) with the right treatment and early is key to improving the health outcomes and long-term survival of patients. One of the ways cancers establish and progress is by blunting the immune defence. This study by Goto et al (2024) has shown that protein, SOX17, helps tumours escape the immune system in early tumour development. SOX17 plays a role in embryonic development and is not usually expressed in the healthy gut lining of adults. The researchers grew mini tumours with common CRC-associated mutations and transplanted them into the colons of mice. The researchers observed an increase in SOX17 expression and decreased cancer-fighting T cells and reduced activity of immune protein, interferon gamma. When the research team generated colorectal tumours that were unable to express SOX17, these tumours became susceptible to the anti-cancer immune response. These findings show that SOX17 is playing a role in the tumours ability to hide from the immune system. The research team validated that human colorectal cancers express SOX17 and, at higher levels in early CRC compared to late stage CRC, suggesting that SOX17 is important for tumour establishment and development by preventing immune surveillance.
Next steps will involve identifying other proteins in this immunosuppressive pathway mediated by SOX17, which may reveal new therapeutic targets. In the bigger picture, it may be important to consider how early CRC and pre-cancerous growths are detected and how we can utilise ‘early’ treatments when they are needed. This study evidences a new immune evasion mechanism facilitated by SOX17 in the early stages of CRC development.