Z Gastroenterol 2015; 53 - A4_3
DOI: 10.1055/s-0035-1568062

Tumor infiltrating B cells producing antitumor active immunoglobulins in resected hepatocellular carcinoma prolong patient survival

SM Brunner 1, T Itzel 4, C Rubner 1, R Kesselring 1, E Griesshammer 1, P Rümmele 2, A Teufel 4, HJ Schlitt 1, S Fichtner-Feigl 1
  • 1University Medical Center Regensburg, Department of Surgery, Regensburg, Germany
  • 2University Medical Center Regensburg, Institute of Pathology, Regensburg, Germany
  • 3University Medical Center Regensburg, Regensburg Center of Interventional Immunology, Regensburg, Germany
  • 4University Medical Center Regensburg, Department of Internal Medicine I, Regensburg, Germany

Background: The immunological microenvironment of hepatocellular carcinoma (HCC) influences patient outcome, however, the role of B cells remains unclear. This study investigated effects of local B-cell infiltration in HCC cohorts on patient survival and immunological and molecular tumor microenvironment.

Methods: Gene expression of 2 independent HCC tissue databases was compared using microarrays. Tissue of resected HCCs was stained for H&E, CD20, CD79a, CD138 and immunoglobulins. Besides histomorphologic evaluation, the immunohistochemical stainings were analysed for the respective cell numbers separately for tumor area, infiltrative margin and distant liver stroma. These findings were correlated with clinical data and patient outcome.

Results: Gene expression analysis of full cancer transcriptomes (N = 2158) revealed an immunological cluster in HCC tissue that mainly contained immunoglobulin fragments. More specifically, in an independent patient cohort (N = 242) that compares HCC with non tumorous liver tissue high expression of these B-cell associated genes was associated with better patient outcome (P = 0.0149). Conclusively, the immunohistochemical analysis of an independent cohort of resected HCC (N = 119) demonstrated that infiltration of HCCs by CD20+ cells (P = 0.004) and CD79a+ cells (P = 0.038) at the infiltrative margin were associated with prolonged patient survival. Further, the immunoglobulin fragments that were identified in the gene expression analysis were detected at high levels in patients with dense B-cell infiltration.

Conclusion: Infiltration of HCCs by B cells is associated with prolonged patient survival. Further, a distinct B-cell like immunoglobulin profile of HCCs was identified that goes along with better patient outcome. We suggest that B cells contribute to local tumor control by secreting increased levels of immunoglobulins with antitumor activity.

Corresponding author: Brunner, Stefan M.

E-Mail: stefan.brunner@ukr.de