4.6 Article

Characterization of immune infiltration in sarcomatoid hepatocellular carcinoma

Journal

AGING-US
Volume 13, Issue 11, Pages 15126-15138

Publisher

IMPACT JOURNALS LLC
DOI: 10.18632/aging.203076

Keywords

sarcomatoid hepatocellular carcinoma; immune infiltration; prognosis

Funding

  1. National Natural Science Foundation of China [81972708, 81773069]
  2. National Key R&D Program of China [2018YFA0109400]
  3. Shanghai RisingStar Program [18QA1401200]
  4. Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai [2018YQ14]

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Sarcomatoid hepatocellular carcinoma (sHCC) is a rare liver malignancy with poorly understood tumor immune features. A study on 31 patients with resected sHCC revealed higher expressions of PD-L1 and B7-H3 in sarcomatoid components, along with higher densities of FOXP3(+) and LAG-3(+) cells and lower CD8(+) cell density compared to conventional HCC components. Higher PD-L1 expression in tumor cells correlated with higher densities of CD8(+), PD-1(+), and LAG-3(+) cells, and was associated with poor overall and disease-free survival in sHCC patients. These findings suggest potential therapeutic targets for immunotherapy in sHCC.
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.

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