Nat Med: Cancer cells can get worse when they spread to the liver, and the team reveals the reasons behind it and proposes treatments

Metastasis is one of the manifestations of many advanced cancers and the most difficult to cure.
, the patient's ability to adhere to cancer cells decreases or even loses completely, while its migration capacity increases, causing cancer cells to move from the native site to other parts of the body with the blood or lymphatic system, eventually forming new tumors.
is even more frightening, in which case the patient is sentenced to death, almost incurable.
, the liver is a common site for cancer metastasis, and clinical studies have shown that cancer patients who spread to the liver tend to show worse prognostication, but the exact mechanism behind this phenomenon has not been explained.
January 4, 2021, the team of professors at the University of Michigan, Zhai Weiping, published a research paper in the journal Nature Medicine entitled: Liver metastasis tablets immunotherapy efficacy via macrophage-mediated T-cell elimination (liver metastasis by macrophage-mediated T-cell elimination inhibits immunotherapy).
study showed that hepatic metastasis tumors can use the host's external immune tolerance mechanism to develop access to immunotherapy resistance through the absence of CD8-T cells.
also found that liver-directed radiotherapy, combined with immunotherapy, restores immune cell function and improves the prognostication of cancer metastasis patients.
it is not clear whether the transfer of cancer cells to specific organs has led to an increase in cancer mortality by impairing systemic anti-tumor immunity and limiting the efficacy of immunotherapy.
liver is a common site for cancer metastasis, and in the case of autoimmune diseases, viral infections and organ transplants, the liver promotes immune tolerance.
mechanisms for immune tolerance to the liver include ineffective immune synapses that cause T-cell ineption, regulatory T-cell induction, or effect T-cell elimination.
, however, the importance of these liver immune tolerance mechanisms is not clearly defined in the context of cancer.
study, the team analyzed data on 718 cancer patients who received immunotherapy at the University of Michigan's Rogel Cancer Center.
these patients are of different cancer types, including non-small cell lung cancer, melanoma, urethra and renal cell carcinoma, and their cancer cells have spread to different organs, such as the liver and lungs.
researchers found that patients with cancer cells spreading to the liver responded worse to immunotherapy -- more cancers throughout the body than similar patients who spread but did not spread to the liver.
, the study's co-author and lead leader, Professor Zhai Weiping, said: "The liver is activating a systemic immunosuppression mechanism that occurs in the liver, but what we're seeing is that it affects the whole body.
more surprising, the researchers found that patients with liver metastasis who received chemotherapy or targeted treatment had no worse prognosis than those who received other types of metastasis.
suggests that patients with cancerous liver metastasis are only insensitive to immunotherapy, which is specific to immunotherapy.
to explore the specific mechanisms of the phenomenon, researchers looked at the microenvironment of liver metastasis tumors and found that tumors were "sucking away" CD8-plus T cells, an immune cell that is used to attack cancer.
, not only are T cells removed from the liver, but an immune desert is created throughout the body.
liver metastasis causes the loss of antigen-specific T-cells throughout the body, which also means that the immune system of patients with hepatic metastasis tumors cannot be activated to fight tumors in any part.
how do we treat patients with liver metastasis? In mouse models of liver metastases, researchers used liver-directed radiation therapy to eliminate immunosuppressive liver macrophages and increase liver T-cell survival.
as T-cells recover, immunosuppressants activate the immune system to eliminate tumors throughout the body.
Radiotherapy reshaping the liver's immune micro-environment and eliminating immunotherapy resistance caused by liver metastasis, the study found that patients with liver metastatic tumors had a poorer immune response and that combined with the liver's immune tolerance mechanisms, radiotherapy and immunotherapy increased patients' T-cell survival, thereby restoring the sensitivity of liver cancer metastasis patients to immunotherapy.
Michael Green, another co-author of the study, said: "Immunotherapy has changed the treatment strategy for many cancers, but cancer patients who have cancer cells transferred to the liver have benefited little from immunotherapy, and this study shows that radiation therapy can be used to reverse this resistance, which has the potential to have a really useful effect on the prognostics of these patients."
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