Scientists at the University of California, San Francisco have uncovered the reason why effective cancer treatments become useless if metastases spread to the liver. The mechanism that makes treatable tumors deadly is reported in an article published in the journal Science Immunology.
Researchers have found that the liver plays an important role in the regulation of immunity, which means that it determines the effectiveness of cancer immunotherapy using checkpoint inhibitors. Checkpoints are a mechanism responsible for suppressing autoimmune processes, but it also inhibits immune cells against tumors.
Cancer cells can produce PD-L1 compounds that turn off regulatory T cells and suppress the immune response against tumors. Some checkpoint inhibitors are directed against the binding of PD-L1 to PD-1, which is a membrane protein and is a checkpoint. The appearance of metastases in the liver, through which a large amount of blood passes, contributes to the dysfunction of antitumor immunity.
Scientists have identified regulatory pathways that make immunotherapy ineffective, and have found that this situation can be corrected by blocking the PD-1 checkpoint while reducing the number of regulatory T cells (Treg) that suppress immunity. Experiments with mice have shown that the liver can be used to “retrain” the immune response against various cancers.