Systemic inflammation influences the prognosis of patients with radically resected non-small cell lung cancer and correlates with the immunosuppressive microenvironment
Peiyu Wang
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Search for more papers by this authorShaodong Wang
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Search for more papers by this authorZewen Sun
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Search for more papers by this authorHao Li
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Search for more papers by this authorYaxing Zhao
Infinity Scope Biotechnology Co. Ltd., Hangzhou, China
Search for more papers by this authorYun Li
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Search for more papers by this authorFan Yang
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Search for more papers by this authorJun Wang
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Search for more papers by this authorKezhong Chen
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Search for more papers by this authorCorresponding Author
Mantang Qiu
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Correspondence
Mantang Qiu and Xiao Li, Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China.
Email: [email protected], [email protected], and [email protected], [email protected]
Search for more papers by this authorCorresponding Author
Xiao Li
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Correspondence
Mantang Qiu and Xiao Li, Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China.
Email: [email protected], [email protected], and [email protected], [email protected]
Search for more papers by this authorPeiyu Wang
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Search for more papers by this authorShaodong Wang
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Search for more papers by this authorZewen Sun
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Search for more papers by this authorHao Li
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Search for more papers by this authorYaxing Zhao
Infinity Scope Biotechnology Co. Ltd., Hangzhou, China
Search for more papers by this authorYun Li
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Search for more papers by this authorFan Yang
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Search for more papers by this authorJun Wang
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Search for more papers by this authorKezhong Chen
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Search for more papers by this authorCorresponding Author
Mantang Qiu
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Correspondence
Mantang Qiu and Xiao Li, Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China.
Email: [email protected], [email protected], and [email protected], [email protected]
Search for more papers by this authorCorresponding Author
Xiao Li
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Beijing, China
Correspondence
Mantang Qiu and Xiao Li, Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, 11 Xizhimen South Street, Beijing 100044, China.
Email: [email protected], [email protected], and [email protected], [email protected]
Search for more papers by this authorAbstract
The impact of host condition on prognosis of non-small cell lung cancer (NSCLC) and the interaction between host and NSCLC remain unclear. This study investigated the association between systemic inflammation and prognosis and characteristics of radically resected NSCLC. This study consisted of a cohort study and an exploratory study of institutional prospective databases. All participants underwent video-assisted thoracoscopic lobectomy as the primary treatment. Systemic inflammation was assessed before surgery using the advanced lung cancer inflammation index and the systemic inflammation response index. Next-generation sequencing and multiplex immunofluorescence analysis were conducted to delineate tumor characteristics. In the cohort study including 1507 participants, high inflammation was associated with poor disease-free survival and overall survival before and after propensity score matching and in multivariable analysis. Systemic inflammation showed good prognostic value for stage IA-IB NSCLC, and the prognostic value diminished with upstaging of NSCLC. In the exploratory study including 217 adenocarcinomas, tumor microenvironment of high inflammation group showed a greater abundance of PDL1+ tumor cells and immune cells, which were independent from driver gene mutations and clinicopathological characteristics. Spatial analysis demonstrated a higher frequency of immune-suppressed cellular neighborhood, increased avoidance between immune cells and PDL1- tumor cells and compromised immune killing and presentation in tumor microenvironment of high inflammation group. Systemic inflammation showed limited association with genomic mutations. Systemic inflammation may influence the prognosis of NSCLC at both the systematic level and the local immune response. The correlation between high inflammation and immunosuppressive microenvironment indicates a novel thread for anticancer treatment.
Graphical Abstract
What's new?
The role of host systemic inflammation in radically-resected non-small cell lung cancer (NSCLC) remains unclear. This study demonstrated baseline systemic inflammation as an independent prognostic factor for early-stage NSCLC after radical resection, with high inflammation being associated with poor disease-free and overall survival. High inflammation also correlated with an immunosuppressive tumor microenvironment, but not with genomic mutations. Systemic inflammation may influence the prognosis of NSCLC not only at the systemic level but also by modulating the local immune response. The revealed interactions between host systemic inflammation and the tumor microenvironment may indicate a novel avenue for anticancer therapy in NSCLC.
CONFLICT OF INTEREST STATEMENT
The authors declare that they have no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
| Filename | Description |
|---|---|
| ijc34547-sup-0001-Tables.xlsxExcel 2007 spreadsheet , 40 KB | Table S1. Broad-panel NGS gene. Table S2. The sequencing coverage and quality statistics of each sample. |
| ijc34547-sup-0002-Supinfo.pdfPDF document, 1.2 MB | Data S1. Supporting Information. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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