An Immunogram for an Individualized Assessment of the Antitumor Immune Response in Patients With Hepatocellular Carcinoma.

Ying Hu,Huaibo Sun,Xianbo Wang,Henghui Zhang

doi:10.3389/fonc.2020.01189

Abstract

In clinical practice, the cancer-immunity cycle of an individual patient with hepatocellular carcinoma (HCC) must be described to support the clinical management of cancer. The present study explored the immunograms of patients with liver cancer based on liver RNA sequencing data to visually display the individualized cancer-immunity cycles. Two independent HCC cohorts [The Cancer Genome Atlas (TCGA) and Liver Cancer-RIKEN, Japan (LIRI-JP) HCC cohorts] with whole exome sequencing (WES) data, RNA sequencing data, and clinical data from TCGA and International Cancer Genome Consortium (ICGC) were enrolled in this study. This study constructed HCC immunograms of cancer immune cells to visually explore the anticancer immune responses of patients with HCC. The patterns of the HCC immunograms were categorized into two clusters: hot and cold HCC immunograms. Favorable overall survival (OS) and disease-free survival (DFS) were observed in the hot immunogram cluster in the TCGA cohort. The results for LIRI-JP cohort were similar to the TCGA cohort. The OS of patients with HCC presenting the hot immunogram was longer than patients with the cold immunogram in the LIRI-JP HCC cohort. Compared with cold immunograms, hot immunograms were characterized by higher levels of immune cell infiltration and stronger immune signatures, including cytolytic activity, IFN-γ signature, immunocostimulator, immunoinhibitor, chemokine, adhesion molecule, MHC I, MHC II, and non-class MHC levels. The main difference in molecular features between hot and cold immunograms was reflected in WNT-CTNNB1 alterations and copy number variant (CNV) and loss of heterozygosity (LOH) scores, which are the molecular features associated with resistance to immunotherapy and tumor escape. The immunogram patterns were distinct in terms of the different molecular features of HCC tumors. The HCC immunogram for the cancer-immune cycle was able to visualize the personalized antitumor immune response of patients with HCC, and the patterns of the HCC immunograms contributed to the clinical outcomes of patients, which may facilitate an individualized assessment of the antitumor immune response for optimal personalized immunotherapy.

Highlights

An evaluation of the cancer-immunity cycle of individual patients is the basis for implementing clinical strategies tailored to each patient
We adopted a cancer immunogram that visually illustrates the state of the cancer-immunity cycle to evaluate the antitumor response in patients with hepatocellular carcinoma (HCC)
Was performed, and the HCC immunograms were separated into two clusters

Summary

Introduction

An evaluation of the cancer-immunity cycle of individual patients is the basis for implementing clinical strategies tailored to each patient. The immunogram for the cancer-immunity cycle integrated all exam and RNA sequencing data, followed by the cloud transformation of the complex omics data in a radar plot to display the immune response of each patient. The steps of the cancer-immunity cycle were assessed using eight axes of the immunogram score (IGS), which included T cell immunity (IGS1), tumor antigenicity (IGS2), priming and activation (IGS3), trafficking and infiltration (IGS4), recognition of tumor cells (IGS5), inhibitor cells (IGS6), checkpoint expression (IGS7), and inhibitory molecules (IGS8). The liver is an immunological organ that contains numerous adaptive and innate immune cells [7]. The immune microenvironment plays a vital role in HCC development

Methods

Results

Conclusion