Effect of regulatory B cell expansion on tissue-resident TPH cells immune evasion in hepatocellular carcinoma.

Abstract

e16252 Background: Within pathologically inflamed nonlymphoid tissues, TPH cells are uniquely positioned to stimulate B cell responses and antibody production. The phenotype, function and clinical relevance of TPH cells in hepatocellular carcinoma (HCC), however, are presently unknown. Methods: Flow cytometry was used to quantify the expression, phenotype and function of TPH cells. Log-rank tests were performed to evaluate disease-free survival and overall survival in samples from 39 patients and 101 patients with HCC. TPH cells, CD19+ B cells and TFH cells were cultured separately in vitro or isolated from C57/B6L mice in vivo for functional assays. Results: TPH cells highly infiltrated in tumor tissues, which influenced tumor sizes and early recurrence predictions and decreased survival times. The tumor-infiltrated TPH cells showed unique ICOShiCXCL13+IL-21-MAF+BCL-6- factors and triggered naïve B cell differentiation into regulatory B cells. Triggering PD-1 induced the production of CXCL13 by TPH cells, which then suppressed tumor-specific immunity and promoted disease progression. Conclusions: Our study reveals a novel regulatory mechanism of TPH cell-regulatory B cell mediated immunosuppression and provides an important perspective for the differentiation balance between protumorigenic TPH cells and antitumorigenic TFH cells in the HCC microenvironment.