Nat Commun: In-tumor immune heterogeneity (ITH): a sign of the development of hepatocellular carcinoma and tumor evolution

Hepatocellular carcinoma (HCC) is a heterogeneous tumor that generally originates from chronic hepatitis and a variety of causes including chronic viral hepatitis, alcoholism and fatty liver disease.
because of the heterogeneity of the disease, its targeted treatment options are limited.
HCC is still the third leading cause of cancer death among the world.
current HCC-related immunotherapy can only increase benefits by 20 percent for patients who respond to PD-1 immune checkpoint blocking (ICB).
, combined therapy with higher clinical efficacy has become a research trend in immunotherapy.
heterogeneity (ITH) in genomic tumors is considered to be an important marker of tumor development and evolution, including HCC.
, however, the biological and clinical relevance of ITH in tumor microencepts (TME) is not clear, based on the spatial distribution of tumor-immersed white blood cells (TILs) and the heterogeneity of esograms.
The remarkable in-tumor heterogeneity (ITH) in the immune environment of liver cancer, given the multi-step nature of the carcinogenic effects and disease development of liver cancer, it is particularly important to study and understand the evolution of its immune micro-environment and the evolution of the tumor genome.
the study aims to fill the knowledge gap in the field of tumor ITH and to study the importance of immune ITH (immune-ITH) in tumor evolution and disease development.
researchers found important spatial and esopic immune ITH in multiple tumor sites and explained its relationship to tumor evolution and disease development in the HCC.
researchers found that immune ITH was associated with tumor transcription group ITH, mutation burden, and unique immune micro-environments.
tumors with low immune ITH experience higher immune selection stress and can cause immune escape through loss of human leucocyte antigen heterolyticity and immune editing.
the transcriptional group immune network was associated with in-tumor immunoheterity (ITH) and replaced by a micro-environment in which tumors with high immune ITH evolved into immunosuppression/depletion.
further studies have shown that this gradient relationship between immune stress and immune ITH is an evolutionary marker of tumors and is closely related to disease progression and immune inseption networks of immune transcription groups.
note that high immune ITH and its transcription group characteristics indicate poor clinical prognostics in HCC patients.
, the results show that with the increase of immune ITH, the immune pattern has been remodeled, and the in-depth study of ITH also provides evidence of tumor-immune co-evolution for the development of HCC.