Intratumoral CD3 and CD8 T-cell densities associated with relapse-free survival in HCC
Cancer Immunology Research
© 2016 American Association for Cancer Research. 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.
Gabrielson, A., Wu, Y., Wang, H., Jiang, J., Kallakury, B., Gatalica, Z., Reddy, S., Kleiner, D., Fishbein, T., Johnson, L., Island, E., Satoskar, R., Banovac, F., Jha, R., Kachhela, J., Feng, P., Zhang, T., Tesfaye, A., Prins, P., Loffredo, C., Marshall, J., Weiner, L., Atkins, M., & He, A. (2016). Intratumoral CD3 and CD8 T-cell densities associated with relapse-free survival in HCC. Cancer Immunology Research, 4 (5). http://dx.doi.org/10.1158/2326-6066.CIR-15-0110