4.5 Article

Immune cell infiltration and immunotherapy in hepatocellular carcinoma

Journal

MATHEMATICAL BIOSCIENCES AND ENGINEERING
Volume 19, Issue 7, Pages 7178-7200

Publisher

AMER INST MATHEMATICAL SCIENCES-AIMS
DOI: 10.3934/mbe.2022339

Keywords

immune cell infiltration; immune microenvironment; immunotherapy; hepatocellular carcinoma; molecular subtype; prognosis

Funding

  1. Project of Education Department in Liaoning Province [LJKZ1133, LNSJYT201917, LNSJYT201910]
  2. Dandong science and Technology Guidance Plan Project [24]
  3. Innovation Training Program for College Students in Liaoning Province [D202103191824376007]

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This study systematically analyzed the immune microenvironment and immune cell infiltration in hepatocellular carcinoma (HCC) and identified three independent immune cell infiltration subtypes with significant survival differences. The study also constructed an immune cell infiltration score model for HCC and identified four genes that accurately predict the subtype based on tumor immune infiltration score. These findings provide theoretical support for accurate immunotherapy strategy in HCC.
Hepatocellular carcinoma is a highly malignant tumor and patients yield limited benefits from the existing treatments. The application of immune checkpoint inhibitors is promising but the results described in the literature are not favorable. It is therefore urgent to systematically analyze the immune microenvironment of HCC and screen the population best suited for the application of immune checkpoint inhibitors to provide a basis for clinical treatment. In this study, we collected The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC)-related data sets to evaluate the immune microenvironment and immune cell infiltration (ICI) in HCC. Three independent ICI subtypes showing significant differences in survival were identified. Further, TCGA-LIHC immunophenoscore (IPS) was used to identify the differentially expressed genes between high-and low-IPS in HCC, so as to identify the immune gene subtypes in HCC tumors. The ICI score model for HCC was constructed, whereby we divided HCC samples into high-and low-score groups based on the median ICI score. The differences between these groups in genomic mutation load and immunotherapy benefit in HCC were examined in detail to provide theoretical support for accurate immunotherapy strategy in HCC. Finally, four genes were screened, which could accurately predict the subtype based on the tumor immune infiltration score. The findings may provide a basis and simplify the process for screening clinical drugs suitable for relevant subgroups.

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