ABSTRACT
The evolution of immune profile from primary tumors to distant and local metastases in non-small cell lung cancer (NSCLC), as well as the impact of the immune background of primary tumors on metastatic potential, remains unclear. To address this, we performed whole-exome sequencing and immunohistochemistry for 73 paired primary and metastatic tumor samples from 41 NSCLC patients, and analyzed the change of immune profile from primary tumors to metastases and involved genetic factors. We found that distant metastases tended to have a decreased CD8+ T cell level along with an increased chromosomal instability (CIN) compared with primary tumors, which was partially ascribed to acquired DNA damage repair (DDR) deficiency. Distant metastases were characterized by immunosuppression (low CD8+ T cell level) and immune evasion (high PD-L1 level) whereas local metastases (pleura) were immune-competent with high CD8+ T cell, low CD4+ T cell and low PD-L1 level. Primary tumors with high levels of CD4+ T cells were associated with distant metastases rather than local metastases. Analysis of TCGA data and a single-cell RNA-sequencing dataset revealed a decreasing trend of major immune cells, such as CD8+ T cells, and an increasing trend of CD4 T helper cells (Th2 and Th1) in primary tumors with metastases from local to distant sites. Our study indicates that there are differences in the immune evolution between distant and local metastases, and that acquired DDR deficiency contributes to the immunosuppression in distant metastases of NSCLC. Moreover, the immune background of primary tumors may affect their metastatic potential.
Disclosure statement
No potential conflict of interest was reported by the authors.
Author contributions
Wen-Fang Tang, Xiao-Jun Fan, Hua Bao, Yi Liang, Rui Fu, Yi-Long Wu and Wen-Zhao Zhong contributed to conception, design of the study, formal analysis and manuscript writing. Wen-Fang Tang and Xiao-Jun Fan contributed to statistical analysis, visualization and manuscript writing. Wen-Fang Tang, Yi Liang, Min Wu, Chao Zhang and Jian Su designed, supervised and provided resources for this study. All authors contributed to manuscript revision, read, and approved the submitted version.
Availability of data and materials
Most data were shown in Supplementary Tables , and other data if need could contact [email protected] or [email protected].
Consent for publication
All authors have approved the publication.
Ethics approval and consent to participate
This study was approved by the ethics and scientific committees of Guangdong Provincial People’s Hospital (no. KY-Q-2022-391-01).
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2023.2215112