Published online Dec 27, 2022. doi: 10.4254/wjh.v14.i12.1997
Peer-review started: September 5, 2022
First decision: September 30, 2022
Revised: October 12, 2022
Accepted: November 22, 2022
Article in press: November 22, 2022
Published online: December 27, 2022
Hepatitis B virus (HBV) infection is a major factor responsible for HBV+ hepatocellular carcinoma (HCC).
An immunological classification of HBV+ HCC may provide both biological in
Based on the enrichment of 23 immune signatures, we identified two immune-specific subtypes (Imm-H and Imm-L) of HBV+ HCC by unsupervised clustering. We showed that this subtyping method was reproducible and predictable by analyzing three different datasets.
Compared to Imm-L, Imm-H displayed stronger immunity, more stromal com
Our data suggest that “hot” tumors have a better prognosis than “cold” tumors in HBV+ HCC and that “hot” tumors respond better to immunotherapy.
Core Tip: First, for the first time, we identified immune-specific subtypes of hepatitis B virus (HBV) + hepatocellular carcinoma (HCC) based on immune signature scores and demonstrated that this new subtyping method was reproducible in three different datasets. Second, our subtyping method captures the comprehensive heterogeneity of HBV+ HCC in the tumor microenvironment, genomic integrity, protein expression profiles, DNA methylation profiles, tumor stemness, intratumor heterogeneity, and clinical outcomes. Third, our data suggest that it is copy number alterations but not tumor mutations responsible for the different immunity between the “hot” and “cold” tumor subtypes in HBV+ HCC. Finally, our identification of the immune-specific subtypes of HBV+ HCC may provide new insights into the tumor biology and identify the HBV+ HCC patients beneficial from immunotherapy.