• IMMUNOTHERAPY
• HEPATOCELLULAR CARCINOMA
• LIVER
• INTEGRINS
• T LYMPHOCYTES

During the past few decades, the field of immuno-oncology has evolved along with the development of novel immunotherapies targeting Foxp3-expressing regulatory T cells (Tregs), a distinctive lineage of CD4⁺ T cells, for patients with cancer. There is considerable experimental and clinical evidence to support the role of Tregs in tumour growth, progression and metastasis, thus favouring suppression of antitumor immune responses and, therefore, immune escape.1 However, its role in cancer is somehow controversial and continues to be studied in order to enlarge the few therapeutic options currently available for patients with metastatic cancer, the majority of which otherwise succumb to the disease.

As of today, the origin and phenotypic characteristics of Tregs remain elusive and so do the mechanisms governing their diversity of functions. To add more fuel to the fire, Tregs possess remarkable adaptability to their local environment and facilitate immune homeostasis through highly specialised tissue-specific pathways.2

In the context of liver metastasis, knowledge of Tregs originated from observations of primary liver cancers, including hepatocellular carcinoma (HCC).3 In fact, liver-derived Tregs are reportedly capable of suppressing both local and extrahepatic antitumour immunity. For cancers where immune checkpoint inhibitors (ICIs) are effective and routinely used, such as melanoma, lung cancer, urothelial and kidney cancers, liver metastasis was associated with a significantly lower response rate to ICI and overall worse survival.4–6

While most of the studies have focused on the role of …