Long Non-Coding RNAs in Lung Cancer: The Role in Tumor Microenvironment.

Shuang Dai,Tao Liu,Ting Liu,Yan-Yang Liu,Feng Luo,Zhi-Wu Wang,Yingying He,Zihan Xu

doi:10.3389/fcell.2021.795874

Abstract

The development of various therapeutic interventions, particularly immune checkpoint inhibitor therapy, have effectively induced tumor remission for patients with advanced lung cancer. However, few cancer patients can obtain significant and long-lasting therapeutic effects for the limitation of immunological nonresponse and resistance. For this case, it’s urgent to identify new biomarkers and develop therapeutic targets for future immunotherapy. Over the past decades, tumor microenvironment (TME)-related long non-coding RNAs (lncRNAs) have gradually become well known to us. A large number of existing studies have indicated that TME-related lncRNAs are one of the major factors to realize precise diagnosis and treatment of lung cancer. Herein, this paper discusses the roles of lncRNAs in TME, and the potential application of lncRNAs as biomarkers or therapeutic targets for immunotherapy in lung cancer.

Highlights

Lung cancer ranks the most important leading cause of cancer-related deaths globally (Bray et al, 2018; Nasim et al, 2019)
In tumor microenvironment (TME), long non-coding RNAs (lncRNAs) can directly or indirectly affect the growth of tumor cells, and play a nonnegligible role in the regulatory recircuit of the immune cells, promoting recruitment of immunosuppressive cells such as Regulatory T cells (Tregs), alternatively activated macrophage (M2)-type macrophages and myeloid-derived suppressor cells (MDSCs), down-regulating the expression of adhesion molecules on endothelial cells, as well as up-regulating of immune checkpoints (PD-1/PD-L1 and CTLA4), which could contribute to tumor development and resistance to drugs or radiotherapy (Fu et al, 2021; Taheri et al, 2021)
We focus on describing how lncRNAs derived from tumor cells, immune cells or exosomes regulate the TME in lung cancer to promote tumor progression, emphasizing the role of these lncRNAs in tumor cells, lymphoid immune cells, macrophages, cancer-related fibroblasts, tumor vasculature and other components of TME (Figure 1)

Summary

Introduction

Lung cancer ranks the most important leading cause of cancer-related deaths globally (Bray et al, 2018; Nasim et al, 2019). In TME, lncRNAs can directly or indirectly affect the growth of tumor cells, and play a nonnegligible role in the regulatory recircuit of the immune cells, promoting recruitment of immunosuppressive cells such as Tregs, M2-type macrophages and myeloid-derived suppressor cells (MDSCs), down-regulating the expression of adhesion molecules on endothelial cells, as well as up-regulating of immune checkpoints (PD-1/PD-L1 and CTLA4), which could contribute to tumor development and resistance to drugs or radiotherapy (Fu et al, 2021; Taheri et al, 2021).

Results

Conclusion