Regulatory T cells in liver metastases: emerging and divergent roles in tumour progression

Liver metastases (LMs) pose a significant burden of morbidity and mortality, resulting in a worse prognosis for many primary malignancies. Despite advancements in cancer treatment, such as immunotherapy, molecular therapies, additional lines of chemotherapy and optimisation of surgical resection, effective therapy against hepatic metastases remains elusive. Recent studies in immuno-oncology have implicated distinct tumour microenvironment (TME) signatures in the hepatic metastatic niche, which interplay with the intrinsic microenvironmental features specific to each primary tumour or organ of origin. Regulatory T cells (Tregs) have been implicated in the immunosuppressive nature of the hepatic TME, yet the exact mechanisms of interaction have not been fully elucidated. Discrepancies in number, function and proportion of Tregs to other tumour-infiltrating lymphocytes have been documented, with conflicting findings in the LMs from different primary tumours. These results may be attributable to the underlying biology of each organ-specific tumour and the unique hepatic TME that forms during the stepwise progression of the metastatic cascade. In this review, we explore the often-contradicting findings of intrahepatic Tregs in LMs from different originating tumours and offer insight into potential mechanisms for these observed differences with implications for future therapeutic strategies.