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- Title
Characterization of pre- and on-treatment soluble immune mediators and the tumor microenvironment in NSCLC patients receiving PD-1/L1 inhibitor monotherapy.
- Authors
Murata, Daiki; Azuma, Koichi; Murotani, Kenta; Kawahara, Akihiko; Nishii, Yuuya; Tokito, Takaaki; Sasada, Tetsuro; Hoshino, Tomoaki
- Abstract
Background: Despite the favorable therapeutic efficacy observed with ICI monotherapy, the majority of non-small cell lung cancer (NSCLC) patients do not respond. Therefore, identifying patients who could optimally benefit from ICI treatment remains a challenge. Methods: Among 183 patients with advanced or recurrent NSCLC who received ICI monotherapy, we analyzed 110 patients whose pre- and post-treatment plasma samples were available. Seventy-three soluble immune mediators were measured at ICI initiation and 6 weeks later. To identify useful biomarkers, we analyzed the association of pre-treatment levels and on-treatment changes of soluble immune mediators with survival of patients. The associations of pre-treatment or on-treatment biomarkers with irAE development, PD-L1 expression, CD8+ TIL density, and neutrophil to lymphocyte ratio (NLR) were also analyzed. Results: Univariate analysis showed that pre-treatment biomarkers included 6 immune mediators, whereas on-treatment biomarkers included 8 immune mediators. Multivariate analysis showed that pre-treatment biomarkers included 4 immune mediators (CCL19, CCL21, CXCL5, CXCL10), whereas on-treatment biomarkers included 5 immune mediators (CCL7, CCL19, CCL23, CCL25, IL-32). IrAE development was associated with on-treatment change in CCL23. PD-L1 expression was associated with the pre-treatment levels of TNFSF13B and the on-treatment change in CCL25. CD8+ TIL density was associated with the pre-treatment CXCL10 level, whereas NLR was correlated with pre-treatment levels of CCL13 and CCL17. Conclusion: We identified several soluble immune mediators as pre-treatment and on-treatment biomarkers of survival in patients with NSCLC treated with ICI monotherapy. Some of these biomarkers were associated with other possible predictors, including irAE development, PD-L1 expression, CD8+ TIL density and NLR. Further large-scale studies are needed to establish biomarkers for patients with NSCLC who received ICI monotherapy.
- Subjects
NEUTROPHIL lymphocyte ratio; NON-small-cell lung carcinoma; IMMUNE checkpoint inhibitors; BIOMARKERS; CHEMOKINES
- Publication
Cancer Immunology, Immunotherapy, 2024, Vol 73, Issue 11, p1
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-024-03781-8