NK Cell immunotherapy in advanced liver cancer cases

Ms. M, who was first diagnosed with hepatocellular carcinoma in her 80s following a hepatitis C infection, underwent successful surgical removal of the tumor. When her cancer recurred in 2016, surgery was no longer recommended given her age. After ruling out radiofrequency ablation, embolization, heavy ion therapy, and proton therapy due to tumor location and physical limitations, her medical team settled on TOMO knife radiotherapy combined with NK cell reinfusion therapy — a gentler systemic approach aimed at improving immunity without the burden of toxic drug side effects.

NK cell reinfusion was timed to follow local radiotherapy on weekends, taking advantage of the 2–3 day high activation window of NK cells after reinfusion. The combination of local radiotherapy and systemic NK cell therapy produced a synergistic anti-cancer effect. Follow-up ultrasound and PET-CT examinations confirmed that the local lesion had disappeared, no metastasis had occurred, and the patient had recovered well with no jaundice or ascites.

NK (natural killer) cells are the immune system's most potent cancer-fighting cells. Unlike T cells, they do not require antigen presentation or assistance from other immune cells — they can independently identify and destroy cancer cells, infected cells, and other abnormal cells on contact. They release toxic particles containing perforin and granzyme onto the target cell membrane, triggering cancer cell self-destruction within as little as 5 minutes. They can also eliminate circulating cancer stem cells, helping to prevent metastasis.

Despite their power, NK cells make up only 5–10% of lymphocytes in peripheral blood, and their numbers and activity decline after the age of 25. In cancer patients, NK cell counts are further reduced, limiting their natural anti-cancer effectiveness. To address this, Japanese scientists developed a multiplication method that extracts 50ml of blood, isolates NK cells, and expands them to 1,000 times their original number — reaching 1 to 5 billion cells — before reinfusing them into the patient, where they circulate throughout the body to target cancer cells systemically.

NK cells are especially relevant to liver cancer because of a unique characteristic of the liver's immune environment. While NK cells account for only 5–10% of lymphocytes in peripheral blood, they make up 30–50% of lymphocytes in the liver — and liver-resident NK cells display higher cytotoxicity against tumor cells compared to circulating NK cells. However, during the development of liver cancer, the proportion and functional activity of these NK cells is significantly reduced, making NK cell therapy a well-matched intervention to restore this depleted defense.

Unlike T cell therapies, NK cell therapy does not cause graft-versus-host disease, making it safe to use cells from closely related donors. There is also a growing body of evidence that NK cell immunotherapy before and after surgery can reduce the risk of cancer recurrence and metastasis.

NK cell therapy is particularly suitable for patients with poor pre-surgical physical condition, those recovering slowly after surgery, patients whose immunity has been weakened by radiotherapy or chemotherapy, and advanced cancer patients for whom conventional treatments are no longer effective. It can be used to improve treatment efficacy, reduce side effects of chemoradiation, relieve cancer pain, improve sleep and quality of life, and extend survival.

The treatment process involves three steps: drawing 30–50ml of peripheral blood from the patient and extracting mononuclear cells; culturing and expanding NK cells in a laboratory over 5–7 days; and reinfusing the expanded NK cells back into the patient like a standard infusion. As the fourth treatment modality after surgery, chemotherapy, and radiotherapy, NK cell therapy represents a meaningful addition to the cancer treatment toolkit — especially for patients seeking a less toxic but still effective approach.