Implications of liver metastasis for cancer immunotherapy

Recent advancements in immuno-oncology enabled the development of immune checkpoint inhibitors to become the first class of drugs that offer complete and durable responses in patients with stage IV metastatic solid tumors. However, potential cures are rare and limited only to certain cancer types. The determinants of the variability of efficacy remain elusive and poorly understood. The immune system could be harnessed to fight against cancer because of its potency, precision, adaptability, and capacity for memory to eradicate tumor cells. As the majority of patients still have low immunotherapy response rates, it is increasingly recognized is that these properties apply to the immune system’s powerful counter-mechanisms to suppress immunity as well. Emerging clinical and preclinical data suggest differences in the pattern of immunotherapy response across tumors in different tissue sites, which has tremendous implications for a treatment’s curative potential. Liver metastasis appears to be reported with increasing frequency at the frontlines of immune-oncology as a predictor of poor response to immunotherapy, and data from translational studies are uncovering distinct mechanisms of treatment resistance derived from the tolerogenic functions of the liver. Recent observations suggest these processes are locally protective of liver tumors and capable of deleterious effects to systemic tumor-specific immunity. Future combination immunotherapy likely will need to consider tissue-specific immune functions for added precision to overcome the challenge of cancer metastasis.

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