Development of a TMErisk model based on immune infiltration in tumour microenvironment to predict prognosis of immune checkpoint inhibitor treatment in hepatocellular carcinoma

Author:

Yan Zi-Jun123,Yu Chu-Ting123,Chen Lei123,Wang Hong-Yang123ORCID

Affiliation:

1. International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Hospital/National Center for Liver Cancer , Shanghai 200438 , PR. China

2. Key Laboratory of Signaling Regulation and Targeting Therapy of Liver Cancer (SMMU), Ministry of Education . Shanghai 200438 , PR. China

3. Shanghai Key Laboratory of Hepatobiliary Tumor Biology (EHBH) , Shanghai 200438 , PR. China

Abstract

AbstractImmune checkpoint inhibitor (ICI) treatment has created the opportunity of improved outcome for patients with hepatocellular carcinoma (HCC). However, only a minority of HCC patients benefit from ICI treatment owing to poor treatment efficacy and safety concerns. There are few predictive factors that precisely stratify HCC responders to immunotherapy. In this study, we developed a tumour microenvironment risk (TMErisk) model to divide HCC patients into different immune subtypes and evaluated their prognosis. Our results indicated that virally mediated HCC patients who had more common tumour protein P53 (TP53) alterations with lower TMErisk scores were appropriate for ICI treatment. HCC patients with alcoholic hepatitis who more commonly harboured catenin beta 1 (CTNNB1) alterations with higher TMErisk scores could benefit from treatment with multi-tyrosine kinase inhibitors. The developed TMErisk model represents the first attempt to anticipate tumour tolerance of ICIs in the TME through the degree of immune infiltration in HCCs.

Funder

National Science Foundation

National Natural Science Foundation of China

Publisher

Oxford University Press (OUP)

Subject

Molecular Biology,Information Systems

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