The inter-link of ageing, cancer and immunity: findings from real-world retrospective study

IF 5.2 2区医学 Q1 GERIATRICS & GERONTOLOGY

Immunity & Ageing Pub Date : 2023-12-15 DOI:10.1186/s12979-023-00399-9

Xiaomin Fu, Peng Qin, Fanghui Li, Huifang Zhu, Hongqin You, Yong Zhang, Benling Xu, Tiepeng Li, Fang Zhang, Lu Han, Lingdi Zhao, Baozhen Ma, Zibing Wang, Quanli Gao

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引用次数: 0

Abstract

Although the concept of declined immune function associated with cancer has been accepted extensively, real-world clinical studies focusing on analysis of the peripheral blood immune changes underlying ageing, immunity and cancer are scarce. In this case-control study, we retrospectively analysed 1375 cancer patients and enrolled 275 age and gender matched healthy individuals. Flow cytometry was conducted to assess the immune changes. Further analysis was examined by SPSS 17.0 and GraphPad Prism 9 software. Cancer patients showed obviously decreased CD3+ T, CD3+CD4+ Th, CD3+CD8+ CTL, CD19+ B, CD16+CD56+ NK cell counts and lower percentage of PD-1 (programmed cell death protein-1, PD-1) positive cells than healthy control (P < 0.0001). For cancer patients, the reference range of circulating percentage of PD-1+CD45+ cells, PD-1+CD3+ T cells, PD-1+CD3+CD4+ Th cells and PD-1+CD3+CD8+ CTL (Cytotoxic T Lymphocyte, CTL) were 11.2% (95% CI 10.8%-11.6%), 15.5% (95% CI 14.7%-16.0%), 15.4% (95% CI 14.9%-16.0%) and 14.5% (95% CI 14.0%-15.5%), respectively. Moreover, the reduction of CD3+ T, CD3+CD4+ Th, CD3+CD8+ CTL, CD19+ B cell counts accompanied with age and stage advancing (P < 0.05). CD16+CD56+ NK cells decreased with stage, but elevated in aged and male cancer patients (P < 0.05). Additionally, the percentage of PD-1 positive cells varied across cancer types, raised with age and stage. Head and neck, pancreatic, gynaecological and lung demonstrated a higher level of the percentage of PD-1 positive cells than melanoma, prostate, and breast cancer (P < 0.05). This study provides the reference range of the percentage of PD-1 positive cells on peripheral blood, confirms the decreased immune cells and a series of immune changes accompanying with cancer, expands our real world evidence to better understand the interactions of ageing, cancer and immunity. Moreover, the circulating percentage of PD-1 positive cells shows similar tumor type distribution with tumor mutational burden (TMB), supports that it maybe a potential predictive biomarker for immune checkpoint inhibitor therapy.

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老龄化、癌症和免疫力之间的相互联系：真实世界回顾性研究的发现

尽管与癌症相关的免疫功能下降的概念已被广泛接受，但侧重于分析衰老、免疫和癌症背后的外周血免疫变化的实际临床研究却很少。在这项病例对照研究中，我们回顾性分析了 1375 名癌症患者，并招募了 275 名年龄和性别匹配的健康人。研究采用流式细胞术评估免疫变化。进一步的分析由 SPSS 17.0 和 GraphPad Prism 9 软件完成。与健康对照组相比，癌症患者的 CD3+ T、CD3+CD4+ Th、CD3+CD8+ CTL、CD19+ B、CD16+CD56+ NK 细胞数量明显减少，PD-1（程序性细胞死亡蛋白-1，PD-1）阳性细胞比例也较低（P < 0.0001）。在癌症患者中，PD-1+CD45+细胞、PD-1+CD3+ T细胞、PD-1+CD3+CD4+ Th细胞和PD-1+CD3+CD8+ CTL（细胞毒性T淋巴细胞，CTL）的循环百分比参考范围分别为11.2%（95% CI 10.8%-11.6%）、15.5%（95% CI 14.7%-16.0%）、15.4%（95% CI 14.9%-16.0%）和14.5%（95% CI 14.0%-15.5%）。此外，CD3+ T、CD3+CD4+ Th、CD3+CD8+ CTL、CD19+ B 细胞数量随着年龄和分期的进展而减少（P < 0.05）。CD16+CD56+ NK细胞随分期而减少，但在老年和男性癌症患者中升高（P < 0.05）。此外，PD-1 阳性细胞的比例在不同癌症类型中各不相同，并随年龄和分期而升高。与黑色素瘤、前列腺癌和乳腺癌相比，头颈癌、胰腺癌、妇科癌和肺癌的 PD-1 阳性细胞百分比水平更高（P < 0.05）。这项研究提供了外周血中 PD-1 阳性细胞百分比的参考范围，证实了免疫细胞的减少以及癌症伴随的一系列免疫变化，为我们更好地理解衰老、癌症和免疫之间的相互作用提供了更多的现实证据。此外，循环中 PD-1 阳性细胞的百分比与肿瘤突变负荷（TMB）显示出相似的肿瘤类型分布，这证明它可能是免疫检查点抑制剂治疗的潜在预测性生物标记物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY

CiteScore

10.20

自引率

3.80%

发文量

期刊介绍： Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.