Profiles of immune infiltration in the tumor microenvironment of hepatocellular carcinoma

Background: Thus far, few studies have systematically analyzed the profiles of immune cells infiltrated in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). Therefore, the purpose of our study was to comprehensively analyze the 22 tumor-infiltrating immune cells (TIICs) and the immune subtypes of HCC, as well as the factors associated with the prognosis of HCC patients. Methods: In this study, we evaluated the abundance of 22 tumor-infiltrating immunocytes of 371 HCC patients from The Cancer Genome Atlas (TCGA) database by using the CIBERSORT algorithm, and defined immune subtypes of HCC according to unsupervised cluster analysis. The immune score of HCC patients was calculated by the prognostic regression model, while the survival analysis was evaluated by the Kaplan-Meier method. In addition, the consistency index of TIICs and principal component analysis (PCA) of immunomodulator genes were estimated. Results: The results of this study showed that three distinct immune subtypes of HCC were stratified, and the C1 subtype and C3 subtype were correlated with a good prognosis. The cellular composition of three immune subtypes was different. Moreover, immunomodulator gene and programmed cell death protein 1/ programmed death-ligand 1 (PD-1/PD-L1) expression in the C1 subtype was significantly higher (P<0.05). Conclusions: This suggested that the low immune score of HCC patients is associated with better clinical outcomes. In addition, the interaction network of cluster of differentiation CD8+ T cells was mainly concentrated in the C1 subtype. Taken together, this study showed that tumor-infiltrating immune cells can perhaps be an important determinant of clinical outcomes of patients with HCC and may provide biomarkers to reflect the immunotherapy response. Notably, the C1 subtype of HCC may be used as an important predictive factor for immunotherapy response.