{"title":"嗜酸性粒细胞作为非小细胞肺癌抗程序性细胞死亡1单药治疗的预测性生物标志物","authors":"Takahiro Uchida, Kazuyuki Nakagome, Kosuke Hashimoto, Hidetoshi Iemura, Yuki Shiko, Atsuto Mouri, Ou Yamaguchi, Yoshitaka Uchida, Yoshiaki Nagai, Tomoyuki Soma, Kyoichi Kaira, Makoto Nagata, Hiroshi Kagamu","doi":"10.3389/fimmu.2025.1574314","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The relationship between eosinophilia and cancer development has recently been investigated. However, the role of eosinophils in tumor immunity, particularly in the context of immune checkpoint inhibitor (ICI) therapy, remains poorly understood.</p><p><strong>Methods: </strong>We investigated the relationship between peripheral blood eosinophil and T-lymphocyte subsets and the clinical characteristics of patients undergoing anti-programmed cell death-1 (PD-1) monotherapy for non-small cell lung cancer (NSCLC). The study included 204 patients treated with nivolumab monotherapy, and clinical data and treatment responses were recorded. PBMCs were collected from 44 out of 204 patients before treatment to analyze T-lymphocyte subsets, focusing on their correlation with blood eosinophils.</p><p><strong>Results: </strong>The percentage of blood eosinophils before nivolumab treatment was positively correlated with the percentage of effector memory subsets in both CD4<sup>+</sup> (r = 0.43, p = 0.0045) and CD8<sup>+</sup> T cells (r = 0.35, p = 0.020). It was negatively correlated with the percentage of naïve subsets of CD4<sup>+</sup> T cells and positively correlated with the percentage of inducible T cell co-stimulator cells among CD8<sup>+</sup> T cells. Patients with higher eosinophil levels (≥1.7%) before nivolumab treatment exhibited significantly longer progression-free survival (log-rank p = 0.014) and overall survival (log-rank p = 0.001) than those with lower eosinophil levels. An early increase in the eosinophil count after treatment was also associated with a better response to nivolumab.</p><p><strong>Conclusion: </strong>Higher blood eosinophil levels may indicate activated T-cell immunity and may be a promising biomarker for the efficacy of anti-PD-1 monotherapy in patients with NSCLC.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1574314"},"PeriodicalIF":5.9000,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537673/pdf/","citationCount":"0","resultStr":"{\"title\":\"Eosinophils as predictive biomarkers in anti-programmed cell death 1 monotherapy for non-small cell lung cancer.\",\"authors\":\"Takahiro Uchida, Kazuyuki Nakagome, Kosuke Hashimoto, Hidetoshi Iemura, Yuki Shiko, Atsuto Mouri, Ou Yamaguchi, Yoshitaka Uchida, Yoshiaki Nagai, Tomoyuki Soma, Kyoichi Kaira, Makoto Nagata, Hiroshi Kagamu\",\"doi\":\"10.3389/fimmu.2025.1574314\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The relationship between eosinophilia and cancer development has recently been investigated. However, the role of eosinophils in tumor immunity, particularly in the context of immune checkpoint inhibitor (ICI) therapy, remains poorly understood.</p><p><strong>Methods: </strong>We investigated the relationship between peripheral blood eosinophil and T-lymphocyte subsets and the clinical characteristics of patients undergoing anti-programmed cell death-1 (PD-1) monotherapy for non-small cell lung cancer (NSCLC). The study included 204 patients treated with nivolumab monotherapy, and clinical data and treatment responses were recorded. PBMCs were collected from 44 out of 204 patients before treatment to analyze T-lymphocyte subsets, focusing on their correlation with blood eosinophils.</p><p><strong>Results: </strong>The percentage of blood eosinophils before nivolumab treatment was positively correlated with the percentage of effector memory subsets in both CD4<sup>+</sup> (r = 0.43, p = 0.0045) and CD8<sup>+</sup> T cells (r = 0.35, p = 0.020). It was negatively correlated with the percentage of naïve subsets of CD4<sup>+</sup> T cells and positively correlated with the percentage of inducible T cell co-stimulator cells among CD8<sup>+</sup> T cells. Patients with higher eosinophil levels (≥1.7%) before nivolumab treatment exhibited significantly longer progression-free survival (log-rank p = 0.014) and overall survival (log-rank p = 0.001) than those with lower eosinophil levels. An early increase in the eosinophil count after treatment was also associated with a better response to nivolumab.</p><p><strong>Conclusion: </strong>Higher blood eosinophil levels may indicate activated T-cell immunity and may be a promising biomarker for the efficacy of anti-PD-1 monotherapy in patients with NSCLC.</p>\",\"PeriodicalId\":12622,\"journal\":{\"name\":\"Frontiers in Immunology\",\"volume\":\"16 \",\"pages\":\"1574314\"},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2025-10-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12537673/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fimmu.2025.1574314\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fimmu.2025.1574314","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:嗜酸性粒细胞增多与癌症发展之间的关系最近被研究。然而,嗜酸性粒细胞在肿瘤免疫中的作用,特别是在免疫检查点抑制剂(ICI)治疗的背景下,仍然知之甚少。方法:研究外周血嗜酸性粒细胞和t淋巴细胞亚群与接受抗程序性细胞死亡-1 (PD-1)单药治疗非小细胞肺癌(NSCLC)患者临床特征的关系。该研究纳入了204例接受纳武单抗单药治疗的患者,记录了临床数据和治疗反应。204例患者中有44例在治疗前收集了pbmc,分析t淋巴细胞亚群,重点关注它们与血液嗜酸性粒细胞的相关性。结果:纳武单抗治疗前血嗜酸性粒细胞百分比与CD4+ (r = 0.43, p = 0.0045)和CD8+ T细胞中效应记忆亚群百分比呈正相关(r = 0.35, p = 0.020)。与CD4+ T细胞naïve亚群百分比呈负相关,与CD8+ T细胞中诱导型T细胞共刺激细胞百分比呈正相关。纳沃单抗治疗前嗜酸性粒细胞水平较高(≥1.7%)的患者比嗜酸性粒细胞水平较低的患者表现出更长的无进展生存期(log-rank p = 0.014)和总生存期(log-rank p = 0.001)。治疗后早期嗜酸性粒细胞计数的增加也与对纳武单抗的更好反应有关。结论:较高的血嗜酸性粒细胞水平可能表明t细胞免疫激活,可能是非小细胞肺癌患者抗pd -1单药治疗疗效的一个有希望的生物标志物。
Eosinophils as predictive biomarkers in anti-programmed cell death 1 monotherapy for non-small cell lung cancer.
Background: The relationship between eosinophilia and cancer development has recently been investigated. However, the role of eosinophils in tumor immunity, particularly in the context of immune checkpoint inhibitor (ICI) therapy, remains poorly understood.
Methods: We investigated the relationship between peripheral blood eosinophil and T-lymphocyte subsets and the clinical characteristics of patients undergoing anti-programmed cell death-1 (PD-1) monotherapy for non-small cell lung cancer (NSCLC). The study included 204 patients treated with nivolumab monotherapy, and clinical data and treatment responses were recorded. PBMCs were collected from 44 out of 204 patients before treatment to analyze T-lymphocyte subsets, focusing on their correlation with blood eosinophils.
Results: The percentage of blood eosinophils before nivolumab treatment was positively correlated with the percentage of effector memory subsets in both CD4+ (r = 0.43, p = 0.0045) and CD8+ T cells (r = 0.35, p = 0.020). It was negatively correlated with the percentage of naïve subsets of CD4+ T cells and positively correlated with the percentage of inducible T cell co-stimulator cells among CD8+ T cells. Patients with higher eosinophil levels (≥1.7%) before nivolumab treatment exhibited significantly longer progression-free survival (log-rank p = 0.014) and overall survival (log-rank p = 0.001) than those with lower eosinophil levels. An early increase in the eosinophil count after treatment was also associated with a better response to nivolumab.
Conclusion: Higher blood eosinophil levels may indicate activated T-cell immunity and may be a promising biomarker for the efficacy of anti-PD-1 monotherapy in patients with NSCLC.
期刊介绍:
Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.