The mechanism early cancer cells employ to evade the immune system

To understand how precancerous growths avoid immune detection, researchers employed a method to cultivate mini colon tumours in a laboratory dish, subsequently implanting them into mice. These tumours were engineered to carry mutated forms of the cancer-associated genes Kras, p53, and APC, commonly found in human colon cancers. Upon implantation in mice, researchers noted a significant upregulation of SOX17 expression within the tumours.

The findings revealed that when SOX17 is activated in cancer cells, it fosters an immunosuppressive environment by inhibiting the synthesis of interferon-gamma receptors, crucial for the immune response against cancer. This prevents cells from neglecting signals for programmed cell death, evading immune attack.

“One of SOX17’s main roles is to turn off the interferon-gamma signalling pathway in colorectal cancer cells and in precancerous adenoma cells. By turning off interferon-gamma receptor signalling in the tumour cells, the tumour cells become hidden from T cells and can grow in the presence of an immune system,” Yilmaz says.

In the absence of interferon-gamma signalling, cancer cells reduce MHC protein production, impeding the display of cancerous antigens to the immune system, and hinder the production of chemokines, which recruit T cells to eliminate the cancerous cells.

Reference: Pelka, K. et al. Spatially organized multicellular immune hubs in human colorectal cancer. Cell DOI: 10.1038/s41586-024-07135-3