肿瘤细胞治疗研究
英文原题：The inter-link of ageing, cancer and immunity: findings from real-world retrospective study.
The inter-link of ageing, cancer and immunity: findings from real-world retrospective study.
本研究提供了外周血PD-1阳性细胞百分比的参考范围，证实了免疫细胞减少以及伴随癌症的一系列免疫变化，扩展了我们的真实世界证据，以更好地理解衰老、癌症和免疫之间的相互作用。
背景：癌症相关免疫功能下降的概念已广为接受，但聚焦分析衰老、免疫和癌症相互作用所致外周血免疫变化的真实世界临床研究仍较少。 方法：本病例对照研究回顾分析了1,375例癌症患者，并纳入275名按年龄和性别匹配的健康个体。采用流式细胞术评估免疫变化，并使用SPSS 17.0和GraphPad Prism 9进行进一步分析。 结果：与健康对照相比，癌症患者CD3+ T、CD3+ CD4+辅助性T（Th）、CD3+ CD8+细胞毒性T（CTL）、CD19+ B和CD16+ CD56+ NK细胞计数明显降低，PD-1（程序性细胞死亡蛋白1）阳性细胞比例也较低（P<0.0001）。癌症患者外周血PD-1+ CD45+、PD-1+ CD3+ T、PD-1+ CD3+ CD4+ Th和PD-1+ CD3+ CD8+ CTL（细胞毒性T淋巴细胞）比例的参考范围分别为11.2%（95%置信区间10.8%–11.6%）、15.5%（95%置信区间14.7%–16.0%）、15.4%（95%置信区间14.9%–16.0%）和14.5%（95%置信区间14.0%–15.5%）。此外，随着年龄增长和疾病分期升高，CD3+ T、CD3+ CD4+ Th、CD3+ CD8+ CTL及CD19+ B细胞计数降低（P<0.05）。CD16+ CD56+ NK细胞随分期升高而减少，但在年龄较大和男性癌症患者中增加（P<0.05）。此外，PD-1阳性细胞比例因癌症类型而异，并随年龄增长及分期升高而增加。头颈癌、胰腺癌、妇科肿瘤和肺癌患者PD-1阳性细胞比例高于黑色素瘤、前列腺癌和乳腺癌患者（P<0.05）。 结论：本研究提供了外周血PD-1阳性细胞比例的参考范围，证实癌症患者免疫细胞减少及一系列伴随癌症出现的免疫变化，扩充了有助于理解衰老、癌症与免疫相互作用的真实世界证据。此外，循环PD-1阳性细胞比例在不同肿瘤类型中的分布与肿瘤突变负荷（TMB）相似，支持其作为免疫检查点抑制剂治疗潜在预测生物标志物的可能性。
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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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