Intratumoral CD3 and CD8 T-cell densities associated with relapse-free survival in HCC

Abstract

Immune cells that infiltrate a tumor may be a prognostic factor for patients who have had surgically resected hepatocellular carcinoma (HCC). The density of intratumoral total (CD3+ ) and cytotoxic (CD8+ ) T lymphocytes was measured in the tumor interior and in the invasive margin of 65 stage I to IV HCC tissue specimens from a single cohort. Immune cell density in the interior and margin was converted to a binary score (0, low; 1, high), which was correlated with tumor recurrence and relapse-free survival (RFS). In addition, the expression of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) was correlated with the density of CD3+and CD8+ cells and clinical outcome. High densities of both CD3+ and CD8+ T cells in both the interior and margin, along with corresponding Immunoscores, were significantly associated with a low rate of recurrence (P ? 0.007) and a prolonged RFS (P ? 0.002). In multivariate logistic regression models adjusted for vascular invasion and cellular differentiation, both CD3+and CD8+ cell densities predicted recurrence, with odds ratios of 5.8 [95% confidence interval (CI), 1.6-21.8] for CD3+ and 3.9 (95% CI, 1.1-14.1) for CD8+ . Positive PD-L1 staining was correlated with high CD3 and CD8 density (P ? 0.024 and 0.005, respectively) and predicted a lower rate of recurrence (P ? 0.034), as well as prolonged RFS (P ? 0.029). Immunoscore and PD-L1 expression, therefore, are useful prognostic markers in patients with HCC who have undergone primary tumor resection.