Turning Cold into Hot: Firing up the Tumor Microenvironment

Qianqian Duan; Hualing Zhang; Junnian Zheng; Lianjun Zhang

doi:10.1016/j.trecan.2020.02.022

Turning Cold into Hot: Firing up the Tumor Microenvironment

Trends Cancer. 2020 Jul;6(7):605-618. doi: 10.1016/j.trecan.2020.02.022. Epub 2020 Mar 21.

Authors

Qianqian Duan¹, Hualing Zhang², Junnian Zheng³, Lianjun Zhang⁴

Affiliations

¹ Suzhou Institute of Systems Medicine, Suzhou, Jiangsu 215123, China; Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, 100005 Beijing, China.
² Department of Gynecology, The Affiliated Hospital of Qingdao University, Qingdao, China.
³ Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China. Electronic address: jnzheng@xzhmu.edu.cn.
⁴ Suzhou Institute of Systems Medicine, Suzhou, Jiangsu 215123, China; Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, 100005 Beijing, China. Electronic address: zlj@ism.cams.cn.

PMID: 32610070
DOI: 10.1016/j.trecan.2020.02.022

Abstract

Cancers develop within complex tissue environments consisting of diverse innate and adaptive immune cells, along with stromal cells, vascular networks, and many other cellular and noncellular components. The high heterogeneity within the tumor microenvironment (TME) remains a key obstacle in understanding and treating cancer. Understanding the dynamic functional interplay within this intricate ecosystem will provide important insights into the design of effective combinatorial strategies against cancer. Here, we present recent technical advances to explore the complexity of the TME. Then, we discuss how innate immune sensing machinery, genetic alterations of oncogenic signaling, cellular metabolism, and epigenetic factors are involved in modulating the TME. Finally, we summarize the potential strategies to boost antitumor immunity by therapeutically exploiting the TME.

Keywords: epigenetic; immune checkpoint blockade; metabolism; single cell profiling; tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Biomarkers, Tumor / antagonists & inhibitors
Biomarkers, Tumor / genetics
Biomarkers, Tumor / immunology
Cell Transformation, Neoplastic / drug effects
Cell Transformation, Neoplastic / immunology*
Combined Modality Therapy / methods
Epigenesis, Genetic / immunology
Ferroptosis / drug effects
Ferroptosis / genetics
Ferroptosis / immunology
Gene Expression Regulation, Neoplastic / drug effects
Gene Expression Regulation, Neoplastic / immunology
Humans
Immune Checkpoint Inhibitors / pharmacology
Immune Checkpoint Inhibitors / therapeutic use
Immunity, Innate / drug effects
Immunity, Innate / genetics
Immunotherapy / methods*
Metabolomics / methods
Neoplasms / diagnosis
Neoplasms / genetics
Neoplasms / immunology
Neoplasms / therapy*
Oncolytic Virotherapy / methods*
Oncolytic Viruses / immunology
RNA-Seq
Signal Transduction / drug effects
Signal Transduction / genetics
Signal Transduction / immunology
Single-Cell Analysis
Tumor Escape / drug effects
Tumor Escape / genetics
Tumor Microenvironment / genetics
Tumor Microenvironment / immunology*

Substances

Biomarkers, Tumor
Immune Checkpoint Inhibitors