A comprehensive analysis of the correlation between plasma cytokines/chemokines and tumor immune microenvironment signature influences the response of checkpoint inhibitors in advanced non-small-cell lung cancer
Issued Date
2026-01-01
Resource Type
eISSN
20500068
Scopus ID
2-s2.0-105027552817
Journal Title
Clinical and Translational Immunology
Volume
15
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Clinical and Translational Immunology Vol.15 No.1 (2026)
Suggested Citation
Mai V.H., Prasanpanich M., Zungsontiporn N., Korphaisarn K., Sitthideatphaiboon P., Aporntewan C., Chantranuwat P., Hirankarn N., Vinayanuwattikun C. A comprehensive analysis of the correlation between plasma cytokines/chemokines and tumor immune microenvironment signature influences the response of checkpoint inhibitors in advanced non-small-cell lung cancer. Clinical and Translational Immunology Vol.15 No.1 (2026). doi:10.1002/cti2.70076 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/114564
Title
A comprehensive analysis of the correlation between plasma cytokines/chemokines and tumor immune microenvironment signature influences the response of checkpoint inhibitors in advanced non-small-cell lung cancer
Corresponding Author(s)
Other Contributor(s)
Abstract
Objectives: Circulating cytokines/chemokines are linked to checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). The tumor-immune microenvironment (TIME) plays a significant role in modulating a broad range of cytokines and chemokines. This study aimed to explore the crosstalk between circulating cytokines/chemokines and TIME, related to ICIs outcomes. Methods: We conducted a prospective cohort study of 81 participants with advanced or recurrent NSCLC who received ICIs. Pretreatment comprehensive 27 cytokines/chemokines analysis, immunohistochemistry (IHC) for CD8, Treg/FOXP3, and PD-L1(22C3) TPS, and RNA sequencing were conducted. Demographic characteristics were integrated in the analysis to define the crosstalk of significant TIME-related signatures. Circulating neutrophil-to-lymphocyte ratio (NLR) and IHC tumor-infiltrated neutrophil density were evaluated to correlate systemic and local inflammatory states with ICIs response. Results: Pretreatment plasma IL-6 and IL-8 were the significant cytokines correlated with surrogate ICIs responses and ICIs progression-free survival (PFS). Despite several correlations between cytokines/chemokines and CD8<sup>+</sup> TILs, Treg/FOXP3<sup>+</sup> TILs, neither pretreatment IL-6 nor IL-8 was correlated with intra-tumoral or stromal Treg/FOXP3<sup>+</sup> TILs, CD8<sup>+</sup> TILs, and PD-L1. Four active neutrophil-related gene signatures overlapped and were significantly correlated with better ICIs outcomes and lower IL-6 levels. Among 69 genes in 4 neutrophil-related gene signatures, the overexpression of TREM1, SORL1, and HSD17B11 significantly contributed and inversely correlated with CIBERSORT memory B cells. Clinically, the stratification by low levels of IL-6/IL-8 and low NLR identified a subgroup with significantly improved survival outcomes, whereas IHC tumor-infiltrated neutrophil counts did not show a similar association. Conclusion: Our study reveals a potential mechanistic axis linking circulating IL-6 and IL-8 to tumor-associated neutrophils, memory B cells, and therapeutic response. These findings underscore the crucial role of synergistic treatment in augmenting the efficacy of ICIs. The crosstalk between neutrophils and B cells in the orchestration of ICIs therapy for NSCLC was further elucidated through the roles of HSD17B11, SORL1, and TREM1.