Decreased granzyme BCD19B cells are associated with tumor progression following liver transplantation.

Lymphocytes play an important role in antitumor immunity following organ transplantation. However, the function of granzyme BCD19B cells on the hepatocellular carcinoma cells from liver transplant recipients remains largely unknown; we aimed to analyze the function and elucidate the mechanisms behind it. Blood samples and clinical data from liver transplant recipients and healthy controls at Beijing Chaoyang Hospital as well as from a validation cohort were collected and analyzed. In this study, we found decreased granzyme BCD19B cells were correlated with early hepatocellular carcinoma recurrence and could further identify liver transplant recipients with poor tumor differentiation, microvascular invasion, increased total tumor diameter, and tumor beyond Milan criteria. Notably, granzyme BCD19B cells directly inhibited the proliferation, migration, and invasion of hepatocellular carcinoma cells. Upon activation regulatory B cells from liver transplant recipients with hepatocellular carcinoma recurrence displayed a CD5CD38CD27CD138CD19 granzyme B phenotype, but the increased expression of CD5, CD38, and CD138, and the decreased protein level and transcriptional level requiring JAK/STAT signaling. In an independent validation cohort, liver transplant recipients with decreased granzyme BCD19B cells had not only early hepatocellular carcinoma cell recurrence but also shorter survival. Our study provides comprehensive data from liver transplant recipients with hepatocellular carcinoma, indicating a critical role of granzyme BCD19B cells in preventing cancer progression. Our findings warrant further investigations for the design of future immunotherapies leading to immune responses and improved patient survival.