Leukocytes infiltration correlates intratumoral microvessel density and influence overall and late-phase disease-free survival in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a severe type of primary liver cancer with high postoperative recurrence. The prognosis predictability of tumor-infiltrating leukocytes (TILs) for patients who underwent HCC resection has been widely reported. However, limited information is available about TIL trafficking, which is also crucial for HCC patients.We included tumor tissue samples and clinical data from 89 HCC patients in this study and performed immunohistochemistry for CD3, CD8, FoxP3, and CD31. TILs were measured using an algorithm for quantification of tumor immune stroma (QTiS). Intratumoral microvessels were counted using Weidner's method. We first examined correlations among them and analyzed their relationships with clinical and survival data.Intratumoral microvessel density (iMVD) was significantly correlated with infiltration of CD3+ (r = 0.338, P = .001) and CD8+ (r = 0.320, P = .002) cells, but not FoxP3+ (r = 0.153, P = .152) cells. After multivariate analysis, higher infiltration of CD3+ (P = .038) independently showed significant predictability on better overall survival after resection of HCC. Although no influence of CD3+ (P = .386) and CD8+ (P = .648) cells were found on general disease-free survival, infiltration of CD3+ (P = .012), tumor size (P = .032) and albumin (P = .007) cells independently predicted late-phase disease-free survival. No significant relationships regarding iMVD, and infiltration of FoxP3+ cells with overall and disease-free survival were found.Our data suggest that increased iMVD could enrich tumor-infiltrating CD3+ cells. Infiltrated CD3+ cells could help to better predict both the overall and late-phase disease-free survival after resection of HCC.