Annals of Surgical Oncology

, Volume 19, Issue 2, pp 455–466

Infiltrating Memory/Senescent T Cell Ratio Predicts Extrahepatic Metastasis of Hepatocellular Carcinoma

  • Qiang Gao
  • Jian Zhou
  • Xiao-Ying Wang
  • Shuang-Jian Qiu
  • Kang Song
  • Xiao-Wu Huang
  • Jian Sun
  • Ying-Hong Shi
  • Bai-Zhou Li
  • Yong-Sheng Xiao
  • Jia Fan
Hepatobiliary Tumors

DOI: 10.1245/s10434-011-1864-3

Cite this article as:
Gao, Q., Zhou, J., Wang, XY. et al. Ann Surg Oncol (2012) 19: 455. doi:10.1245/s10434-011-1864-3

Abstract

Background

The density of tumor-infiltrating immunocytes (TICs) has been proposed as an independent predictor of intrahepatic recurrence in patients with hepatocellular carcinoma (HCC). However, the relative roles of TIC density in predicting tumor extrahepatic metastasis remain to be elucidated.

Methods

The densities of CD3+, CD8+, granzyme B+, FoxP3+, CD45RO+, CD20+, CD1a+, CD83+, CD57+, and CD68+ TICs were assessed by immunohistochemistry in tissue microarrays containing paired intratumoral (IT) and peritumoral (PT) tissues from 206 consecutive HCC patients who underwent liver transplantation. Occurrence of extrahepatic metastasis, recurrence-free survival (RFS), and cancer-specific survival (CSS) were assessed retrospectively in relation to TIC densities.

Results

CD45RO+ memory T cell density was lower in tumor tissue compared with peritumor, whereas CD57+ senescent T cell density was higher. Univariate analysis revealed that increased CD45ROIT+ and decreased CD57PT+ densities were statistically significantly associated with favorable RFS and CSS, while other types of TICs, intratumorally or peritumorally, showed no prognostic values. Further, the CD45ROIT+/CD57PT+ ratio could stratify patients more accurately in terms of RFS and CSS than either marker used alone. Finally, multivariate analysis indicated that a high CD45ROIT+/CD57PT+ ratio was independently associated with better RFS (hazard ratio [HR] = 0.64; 95% confidence interval [CI], 0.42 to 0.98; P = 0.040) and CSS (HR = 0.51; 95% CI, 0.31 to 0.83; P = 0.007), but not CD45ROIT+ or CD57PT+ individually.

Conclusions

These results suggest that the CD45ROIT+/CD57PT+ (memory/senescent T cell) ratio is of vital importance in preventing HCC extrahepatic metastasis and in particular demonstrates its independent prognostic value in liver transplant recipients.

Supplementary material

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Copyright information

© Society of Surgical Oncology 2011

Authors and Affiliations

  • Qiang Gao
    • 1
  • Jian Zhou
    • 1
    • 2
    • 3
  • Xiao-Ying Wang
    • 1
  • Shuang-Jian Qiu
    • 1
  • Kang Song
    • 1
  • Xiao-Wu Huang
    • 1
  • Jian Sun
    • 1
  • Ying-Hong Shi
    • 1
  • Bai-Zhou Li
    • 4
  • Yong-Sheng Xiao
    • 1
  • Jia Fan
    • 1
    • 2
    • 3
  1. 1.Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical SchoolFudan UniversityShanghaiPeople’s Republic of China
  2. 2.Cancer Center, Institute of Biomedical SciencesFudan UniversityShanghaiPeople’s Republic of China
  3. 3.Shanghai Key Laboratory of Organ Transplantation, Zhongshan HospitalFudan UniversityShanghaiPeople’s Republic of China
  4. 4.Department of Pathology, The 2nd Affiliated HospitalZhejiang University College of MedicineHangzhouPeople’s Republic of China