Research Paper Volume 13, Issue 11 pp 15126—15138

Characterization of immune infiltration in sarcomatoid hepatocellular carcinoma

Chubin Luo1,2, *, , Haoyang Xin1,2, *, , Dan Yin1,2, *, , Tongyi Zhao1,2, , Zhiqiang Hu1,2, , Zhengjun Zhou1,2, , Rongqi Sun1,2, , Na Yao1,2, , Qiman Sun1,2, , Jia Fan1,2, , Xiaowu Huang1,2, , Jian Zhou1,2, , Shaolai Zhou1,2, ,

  • 1 Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
  • 2 Key Laboratory of Carcinogenesis and Cancer Invasion, Fudan University, Shanghai 200032, China
* Equal contribution

Received: November 3, 2020       Accepted: April 29, 2021       Published: June 3, 2021
How to Cite

Copyright: © 2021 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Sarcomatoid hepatocellular carcinoma (sHCC) is a rare type of liver malignancy. Currently, the tumor immune features of sHCC are poorly understood. We recruited 31 patients with resected sHCC for whom tissue samples and complete clinicopathologic and follow-up data were available. To understand the immune infiltration of sHCC, immunohistochemical staining was performed on the resected sHCC samples to compare the expressions of programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), B7-H3, indoleamine 2,3-dioxygenase (IDO), lymphocyte-activation gene 3 (LAG-3), CD8, FOXP3, and CD68 in tumor and peritumoral tissues. Kaplan-Meier and Cox regression analyses were used to assess the predictive value of immune markers. Sarcomatoid components were characterized with significantly higher expression of PD-L1 and B7-H3 in tumor cells than in conventional HCC components, as well as in peritumoral tissue. Additionally, sarcomatoid components had a higher density of FOXP3+ and LAG-3+ cells and a lower density of CD8+ cells than conventional HCC components or peritumoral tissue. Higher expression of PD-L1 in tumor cells significantly correlated with higher densities of CD8+, PD-1+, and LAG-3+ cells. Increased tumor PD-L1 expression and decreased CD8+ T-cell density were associated with poor overall survival (OS) and disease-free survival (DFS) in patients of sHCC. These findings suggest further characterization on relative mechanism of sHCC immune infiltration may identify therapeutic targets for immunotherapy.


sHCC: Sarcomatoid hepatocellular carcinoma; PD-1: Programmed death-1; PD-L1: Programmed death-ligand 1; IDO: Indoleamine 2,3-dioxygenase; LAG-3: Lymphocyte activating 3; TAM: Tumor-associated macrophages; CI: Confidential interval; OS: Overall survival; DFS: Disease-free survival.