Deciphering the Immune-Tumor Interplay During Early-Stage Lung Cancer Development via Single-Cell Technology.

Wei-Wei Chen,Chang Chen,Yingze Li,Jun Wang,Guangsuo Wang,Yijiu Ren,Hanjie Li,Wei Liu

doi:10.3389/fonc.2021.716042

Abstract

Lung cancer is the leading cause of cancer-related death worldwide. Cancer immunotherapy has shown great success in treating advanced-stage lung cancer but has yet been used to treat early-stage lung cancer, mostly due to lack of understanding of the tumor immune microenvironment in early-stage lung cancer. The immune system could both constrain and promote tumorigenesis in a process termed immune editing that can be divided into three phases, namely, elimination, equilibrium, and escape. Current understanding of the immune response toward tumor is mainly on the “escape” phase when the tumor is clinically detectable. The detailed mechanism by which tumor progenitor lesions was modulated by the immune system during early stage of lung cancer development remains elusive. The advent of single-cell sequencing technology enables tumor immunologists to address those fundamental questions. In this perspective, we will summarize our current understanding and big gaps about the immune response during early lung tumorigenesis. We will then present the state of the art of single-cell technology and then envision how single-cell technology could be used to address those questions. Advances in the understanding of the immune response and its dynamics during malignant transformation of pre-malignant lesion will shed light on how malignant cells interact with the immune system and evolve under immune selection. Such knowledge could then contribute to the development of precision and early intervention strategies toward lung malignancy.

Highlights

As a life-threatening disease, lung cancer was estimated to cause more than 1.8 million deaths per year all over the world, with a 5-year survival rate of less than 20% [1]
The driver mutations, chromosomal copy number aberrations, and abnormal epigenetic events in tumor cells work together to influence host immune responses [56]. These results reveal that the early development of lung cancer is a continuous and gradual process modulated by the immuneediting mechanism (Figure 1)
McGranahan et al demonstrated the positive association of high tumor mutation burdens with more activated CD8+ T cells and higher levels of PDL1 expression in early-stage non-small cell lung cancer (NSCLC) [78]

Summary

INTRODUCTION

As a life-threatening disease, lung cancer was estimated to cause more than 1.8 million deaths per year all over the world, with a 5-year survival rate of less than 20% [1]. Many therapies, including chemotherapy, radiosurgery, targeted therapy, and immunotherapy, have been applied for lung cancer treatment, the 5-year survival rate is only 50% for patients with early-stage lung cancer [7]. All aspects of the cell, including a full history of its molecular states, spatial positions, and environmental interactions can be examined at the level of single cell by multimodal technologies and integrated computational methods [27] These methods demonstrated the power of simultaneously characterizing multiple levels of the immune response, which may boost our understanding of the underlying molecular mechanisms on how tumor evolves, and contribute to the early detection and treatment of lung cancer by aiding the rational design of innovative diagnostic and personalized management approaches for patients [28, 29] (Table 1).

Conclusions

CONCLUSION AND PERSPECTIVE