Researchers at Zhongshan University have uncovered a surprising new way that a popular cancer immunotherapy works. In a study published in Cancer Cell, they showed that blocking the PD‑1 checkpoint not only revives T‑cells, as previously thought, but also awakens B‑cells that produce powerful antibodies against hepatitis B virus (HBV) inside liver tumors. These antibodies gather in tiny immune hubs called tertiary lymphoid structures, bind to HBV proteins released by cancer cells, and trigger the complement system to kill the tumor. The team examined patients with recurrent hepatocellular carcinoma (HCC) undergoing anti‑PD‑1 treatment before surgery and identified two patterns of immune response: one driven by T‑cells and another dominated by B‑cells. In the B‑cell‑rich group, high‑affinity anti‑HBV antibodies dramatically improved tumor control in mouse models and appeared to boost the drug’s effectiveness in humans. This discovery turns the virus that often causes liver cancer into a new target for immune attack, suggesting that combining anti‑PD‑1 drugs with therapies that enhance HBV‑specific antibodies could become a personalized strategy to prevent cancer recurrence. The findings open a fresh avenue for treating HBV‑related liver cancer and may reshape future immunotherapy trials.
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