SOX17: a new therapeutic target for immune evasion of colorectal cancer.

Abstract

Despite advances in cancer immunotherapies across various cancers, survival outcomes in colorectal cancer (CRC) with these agents remain largely unsatisfactory despite the high tumour burden. Colorectal stem cells (CSCs), especially LGR5+ CSCs, are the significant drivers in CRC initiation, progression and resistance to conventional therapies. Although native immune surveillance is sufficient to combat early tumour formation, CRC evades early immune detection with its well-documented adenoma-to-carcinoma sequence. The exact mechanism underlying this phenomenon still needs to be better understood. SRY-related HMG box gene 17 (SOX17), a transcription factor that specifies embryonic gut formation, is increasingly recognised as a significant factor in CRC tumourigenesis. However, its role as a tumour suppressor or oncogene is still debated. Evidence from a recent study highlighted the critical role of SOX17 in reshaping the tumour immune ecosystem through the simultaneous inhibition of CD8+ T cells and selective suppression of LGR5 expression in CSCs through transcriptional repression, thereby facilitating disease progression. Given its role in immune evasion, SOX17 could be a promising marker in personalised therapy. Additionally, SOX17 could play a role in the diagnostic arena, potentially identifying dysplasia in the gastrointestinal tract. Future clinical, basic and genetic studies focusing on SOX17 are needed to ascertain its mechanistic role in tumour immunomodulation in CRC and diagnosing preneoplastic lesions in the gastrointestinal tract.