T- and B-Cells in the Inner Invasive Margin of Hepatocellular Carcinoma after Resection Associate with Favorable Prognosis

Abstract

In this retrospective study on 67 patients with hepatocellular carcinoma (HCC), after tumor resection, we evaluated the significance of CD3+ and CD8+ T-lymphocytes and CD20+ B-lymphocytes in tumor and non-tumor liver for time to recurrence (TTR), disease-free survival (DFS) and overall survival. After immunohistochemical staining, the density of nucleated lymphocyte profiles (QA) was estimated stereologically in the tumor center (TC), inner margin (inn M), outer margin (out M), peritumor and non-tumor liver. In TC, intermediate and high QA of CD8+ cells predicted longer TTR, whereas CD3+ and CD20+ were predictive only at high QA. DFS was predicted by high QA of CD3+, CD8+ and CD20+ cells in TC. The inn M harbored smaller QA of CD3+, CD8+ and CD20+ lymphocytes than out M. In contrast to out M, high T-cells’ QA and intermediate and high B-cell QA in inn M predicted longer TTR and DFS. High inn M/out M QA ratios of CD3+ and CD20+ cells were associated with longer TTR and DFS, whereas high inn M/out M QA ratio of CD8+ was predictive only for DFS. Patients with intermediate-high QA of combined CD8+ and CD20+ cells in inn M showed longer TTR and DFS, compared to CD8+-high or CD20+-high alone. Our findings highlight overall heterogeneity of the tumor invasive margin, the importance of inn M, and the predictive role of B-cells.