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Abstract：
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.
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.
摘要：
背景：尽管与癌症相关的免疫功能下降的概念已被广泛接受，真实世界的临床研究，重点是分析衰老背后的外周血免疫变化，免疫力和癌症很少。
方法：在本病例对照研究中，我们回顾性分析了1375例癌症患者,纳入了275例年龄和性别相匹配的健康个体.进行流式细胞术以评估免疫变化。通过SPSS17.0和GraphPadPrism9软件检查进一步的分析。
结果：癌症患者的CD3+T明显下降，CD3+CD4+Th,CD3+CD8+CTL,CD19+B,CD16+CD56+NK细胞计数和PD-1(程序性细胞死亡蛋白-1,PD-1)阳性细胞的百分比低于健康对照(P<0.0001)。对于癌症患者，PD-1+CD45+细胞循环百分比的参考范围，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）为11.2%（95%CI10.8%-11.6%），15.5%（95%CI14.7%-16.0%），15.4%（95%CI14.9%-16.0%）和14.5%（95%CI14.0%-15.5%），分别。此外，CD3+T的减少，CD3+CD4+Th,CD3+CD8+CTL,CD19+B细胞计数与年龄和分期有关(P<0.05)。CD16+CD56+NK细胞随分期降低,但在老年和男性癌症患者中升高(P<0.05)。此外,PD-1阳性细胞的百分比因癌症类型而异，随着年龄和阶段的增长。头部和颈部,胰腺,妇科和肺部显示PD-1阳性细胞的百分比高于黑色素瘤，前列腺,乳腺癌(P<0.05)。
结论：本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和一系列伴随癌症的免疫变化，扩展我们现实世界的证据来更好地理解衰老的相互作用，癌症和免疫力此外，PD-1阳性细胞的循环百分比显示与肿瘤突变负荷（TMB）相似的肿瘤类型分布，支持它可能是免疫检查点抑制剂治疗的潜在预测生物标志物。
方法：在本病例对照研究中，我们回顾性分析了1375例癌症患者,纳入了275例年龄和性别相匹配的健康个体.进行流式细胞术以评估免疫变化。通过SPSS17.0和GraphPadPrism9软件检查进一步的分析。
结果：癌症患者的CD3+T明显下降，CD3+CD4+Th,CD3+CD8+CTL,CD19+B,CD16+CD56+NK细胞计数和PD-1(程序性细胞死亡蛋白-1,PD-1)阳性细胞的百分比低于健康对照(P<0.0001)。对于癌症患者，PD-1+CD45+细胞循环百分比的参考范围，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）为11.2%（95%CI10.8%-11.6%），15.5%（95%CI14.7%-16.0%），15.4%（95%CI14.9%-16.0%）和14.5%（95%CI14.0%-15.5%），分别。此外，CD3+T的减少，CD3+CD4+Th,CD3+CD8+CTL,CD19+B细胞计数与年龄和分期有关(P<0.05)。CD16+CD56+NK细胞随分期降低,但在老年和男性癌症患者中升高(P<0.05)。此外,PD-1阳性细胞的百分比因癌症类型而异，随着年龄和阶段的增长。头部和颈部,胰腺,妇科和肺部显示PD-1阳性细胞的百分比高于黑色素瘤，前列腺,乳腺癌(P<0.05)。
结论：本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和一系列伴随癌症的免疫变化，扩展我们现实世界的证据来更好地理解衰老的相互作用，癌症和免疫力此外，PD-1阳性细胞的循环百分比显示与肿瘤突变负荷（TMB）相似的肿瘤类型分布，支持它可能是免疫检查点抑制剂治疗的潜在预测生物标志物。
