"Nature" published an article by Peking University to reveal the immune microenvironment subtypes of liver cancer

The Zhang Ning team of the Cancer Translational Research Center of Peking University First Hospital worked closely with the team of Zhang Zemin of the Biomedical Frontier Innovation Center (BIOPIC) of Peking University and the team of Zhu Jiye of the Department of Hepatobiliary Surgery of Peking University People's Hospital Nature) published a research paper entitled "Liver tumor immune microenvironment subtypes and neutrophil heterogeneity.
"
This research system revealed the immune microenvironment subtypes of liver cancer, and deeply resolved the functional heterogeneity of tumor-associated neutrophils, and finally demonstrated that targeting tumor-associated neutrophils was expected to form a new immunotherapy strategy
for liver cancer through mouse liver cancer models.

Screenshot of the paper

The heterogeneity of the immune microenvironment is one of
the important reasons for tumor resistance, recurrence and poor prognosis.
In recent years, immunotherapy and related combination therapy regimens have brought hope to patients with advanced tumors, and systematic exploration of the heterogeneity of tumor immune microenvironment has played an important guiding role in treatment selection, efficacy prediction, protocol optimization and development of new immunotherapy targets
.
However, there is still a lack of systematic understanding of the heterogeneity of the immune microenvironment of liver cancer, and there is an urgent need for unbiased research strategies that include all cell subtypes to systematically reveal the heterogeneity of
the immune microenvironment of liver cancer.

In the study, the researchers collected 160 samples from 124 cases and 29 fresh tissue samples from 8 mice to complete antibody-enriched, single-cell transcriptome sequencing
for a total of 189 samples 。 At the same time, the researchers performed exome sequencing on 84 supporting cases, and collected 8 published single-cell transcriptome sequencing datasets, 453 tissue transcriptome sequencing and 10 spatial transcriptome data for comprehensive analysis, and comprehensively used tumor cell lines to construct the In vitro culture system, based on clinical samples to construct the Ex vivo experimental system, and the In vivo experimental system based on mouse tumor models for comprehensive verification
.

Illustration of the paper

This study defines for the first time the five immune microenvironment subtypes (TIMELASER) of liver cancer at single-cell accuracy, explores its cell composition, spatial distribution, genomic characteristics and chemokine receptor-ligand network, and comprehensively reveals the heterogeneity of tumor-associated neutrophils (TAN) for the first time, discovers and verifies the tumor-promoting mechanism of two key subsets of CCL4+ and PD-L1+TAN, and studies the construction of mouse liver cancer models from In vitro, Exvivo, In Vivo has gradually proved that targeting tumor-associated neutrophils is expected to form a new liver cancer immunotherapy regimen
at three levels.
The findings suggest that interventions targeting tumor-associated neutrophils are expected to significantly increase the number
of patients effectively treated by immune checkpoints.
These results provide key information
for basic research and clinical diagnosis and treatment of liver cancer and even solid tumors.

XUE RUIDONG, ASSOCIATE RESEARCHER OF PEKING UNIVERSITY FIRST HOSPITAL, DR.
ZHANG QIMING OF PEKING UNIVERSITY BIOPIC, CAO QI, DOCTORAL CANDIDATE OF PEKING UNIVERSITY FIRST HOSPITAL, ASSOCIATE RESEARCHER KONG RUIRUI OF PEKING UNIVERSITY FIRST HOSPITAL AND DR.
XIANG XIAO OF PEKING UNIVERSITY PEOPLE'S HOSPITAL ARE THE JOINT FIRST AUTHORS
OF THE PAPER.
Zhang Ning, Zhang Zemin and Zhu Jiye are co-corresponding authors
.
The research has been supported and funded
by many national science foundations, such as the National Natural Science Foundation of China, the National Science and Technology Major Project of the 13th Five-Year Plan, the National Key Research and Development Program, and the Basic Science Center.

Expert profiles

Jiye Zhu, chief physician, professor, doctoral supervisor, expert in liver surgery and liver transplantation
.
Director of the Institute of Organ Transplantation, Peking University, Director of the Liver Cancer Diagnosis and Treatment Center of Peking University, and Director of
the Organ Transplantation Center of Peking University People's Hospital.