Prognostic Significance of Plasma Neutrophil Extracellular Trap Levels in Patients with Non-Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors.

Autor:	Horaguchi S; Cancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan.; Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan.; Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan., Nakahara Y; Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama 241-8515, Japan.; Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara 252-0375, Japan., Igarashi Y; Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan., Kouro T; Cancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan.; Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan., Wei F; Cancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan.; Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan., Murotani K; Biostatistics Center, Kurume University School of Medicine, Kurume 830-0011, Japan., Udagawa S; Mathematics Section, Division of Natural Sciences, Nihon University School of Medicine, Tokyo 173-0032, Japan., Higashijima N; Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan., Matsuo N; Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan., Murakami S; Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama 241-8515, Japan., Kato T; Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama 241-8515, Japan., Kondo T; Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama 241-8515, Japan., Xiang H; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan., Kasajima R; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan., Himuro H; Cancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan.; Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan., Tsuji K; Cancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan.; Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan., Mano Y; Cancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan.; Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan., Komahashi M; Cancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan.; Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan.; Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan., Miyagi Y; Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan., Saito H; Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama 241-8515, Japan., Azuma K; Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume 830-0011, Japan., Uehara S; Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan., Sasada T; Cancer Vaccine and Immunotherapy Center, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan.; Division of Cancer Immunotherapy, Kanagawa Cancer Center Research Institute, Yokohama 241-8515, Japan.
Jazyk:	angličtina
Zdroj:	Biomedicines [Biomedicines] 2024 Aug 12; Vol. 12 (8). Date of Electronic Publication: 2024 Aug 12.
DOI:	10.3390/biomedicines12081831
Abstrakt:	Neutrophil extracellular traps (NETs) released from neutrophils are related to cancer progression. However, the relationship between the therapeutic effects of immune checkpoint inhibitors (ICIs) such as anti-PD-1 and anti-PD-L1 antibodies and plasma NET concentration in patients with non-small cell lung cancer (NSCLC) is poorly understood. In this study, concentrations of citrullinated histone H3 (CitH3), a surrogate marker of NETs, in plasma before/after treatment were examined in patients with advanced or recurrent NSCLC undergoing ICI treatment (n = 185). The clinical significances of NET levels before/after treatment and posttreatment changes were statistically evaluated. As a result, multivariate Cox analysis showed that high NET levels before treatment were statistically significant predictors of unfavorable overall survival (OS; p < 0.001, HR 1.702, 95% CI 1.356-2.137) and progression-free survival (PFS; p < 0.001, HR 1.566, 95% CI 1.323-1.855). The Kaplan-Meier curves showed significant separation between the high- and low-NET groups in OS ( p = 0.002) and PFS ( p < 0.001). Additionally, high NET levels after treatment were also significantly associated with worse OS ( p < 0.001) and PFS ( p < 0.001) by multivariate Cox analysis. Notably, the pretreatment NET levels were significantly correlated with the plasma levels of NET-related inflammatory cytokines, such as IL-6 and IL-8, and with NET-related gene expression and immune-suppressive profile in peripheral blood mononuclear cells. Our findings suggest that NETs released from activated neutrophils might reduce the clinical efficacy of ICIs in patients with NSCLC.
Databáze:	MEDLINE
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