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Cancer Immunol Res. 2016 May;4(5):419-30. doi: 10.1158/2326-6066.CIR-15-0110. Epub 2016 Mar 11.

Intratumoral CD3 and CD8 T-cell Densities Associated with Relapse-Free Survival in HCC.

Author information

1
Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia.
2
First Hospital of Hunan University of Chinese Medicine, Changsha City, Hunan Province, People's Republic of China.
3
Department of Pathology, Georgetown University Hospital, Washington, District of Columbia.
4
Caris Life Science, Irving, Texas.
5
Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
6
Medstar Transplant Institute, Georgetown University Hospital, Washington, District of Columbia.
7
Department of Surgery, Georgetown University Hospital, Washington, District of Columbia.
8
Department of Radiology, Georgetown University Hospital, Washington, District of Columbia.
9
Georgetown Lombardi Comprehensive Cancer Center, Division of Hematology and Oncology, Washington, District of Columbia. arh29@georgetown.edu.

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. Cancer Immunol Res; 4(5); 419-30.

PMID:
26968206
PMCID:
PMC5303359
DOI:
10.1158/2326-6066.CIR-15-0110
[Indexed for MEDLINE]
Free PMC Article

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