乙型肝炎性肝癌患者肿瘤微环境中淋巴细胞浸润情况及其临床意义

Lymphocyte infiltration in tumor microenvironment of patients with HBV infected liver cancer and its clinical significance

目的探讨乙型肝炎性肝癌患者肿瘤微环境中淋巴细胞浸润情况及其临床意义。方法前瞻性纳入内蒙古医科大学附属医院2014年1月至2016年1月收治的乙型肝炎(HBV)性肝癌患者40例作为研究组,同期收集非肝炎性肝癌患者40例作为对照组。观察两组患者肿瘤微环境中CD4^+T细胞、CD8^+T细胞、Treg细胞水平,以及外周血中IL-2、IL-10、TGF-β水平。同时观察HBV DNA病毒载量与免疫指标的相关性。结果与对照组比较,研究组患者CD4+T细胞水平显著升高[(21.08±3.12)%vs(19.72±2.89)%,P=0.047],CD8+T细胞水平显著降低[(28.83±2.52)%vs(30.07±2.41)%,P=0.027],Treg细胞水平显著升高[(8.12±1.47)%vs(6.62±1.42)%,P<0.001];IL-2水平显著降低[(15.48±4.30)pg/m L vs(27.28±5.95)pg/m L,P<0.001),IL-10水平显著升高[(36.39±7.69)pg/m L vs(29.82±6.17)pg/m L,P<0.001),TGF-β水平显著升高[(31.95±3.72)pg/m L vs(23.49±3.83)pg/m L,P<0.001)。Pearson线性相关性分析显示,HBV DNA病毒载量与CD8+T细胞及IL-2水平负相关,与CD4+T细胞、Treg和TGF-β水平正相关(P<0.05)。结论乙型肝炎性肝癌患者肿瘤组织微环境中淋巴细胞失衡,且与HBV DNA病毒载量有关。

Objective To investigate the lymphocyte infiltration in tumor microenvironment of patientswith hepatitis B virus （HBV） infected liver cancer and its clinical significance. Methods A total of 40 patientswith HBV infected liver cancer between Jan. 2014 and Jan. 2016 were selected as a study group and 40 patientswith non-virus infected liver cancer were collected as a control group. The CD4＋T cells, CD8＋T cells and Tregin the tumor microenvironment of the both groups were compared, as well as the IL-2, IL-10 and TGF-β levelsin the peripheral blood. Moreover, the association between HBV DNA viral loading and immune indexes werestudied as well. Results When compared with the control group, patients in the study group got a significantlyhigher level of CD4＋T [（21.08±3.12）% vs （19.72±2.89）%, P=0.047）, a decrease in CD8＋T cell [（28.83±2.52）%vs （30.07±2.41）%, P=0.027）, an elevated level of Treg [（8.12±1.47）% vs （6.62±1.42）%, P〈0.001）; a decreasein IL-2 [（15.48±4.30） pg/mL vs （27.28±5.95）pg/mL, P〈0.001）, a higher level of IL-10 [（36.39±7.69） pg/mL vs（29.82±6.17） pg/mL, P〈0.001）, and an increase in TGF-β [（31.95±3.72） pg/mL vs （23.49±3.83） pg/mL, P〈0.001）.Pearson linear correlation analysis showed that the viral loading of HBV DNA was negatively correlated withCD8＋T cells and IL-2, positively correlated with CD4＋T cells, Treg and TGF-β （P〈0.05）. Conclusion The lymphocytesof tumor microenvironment in patients with HBV infected liver cancer is imbalanced and related to theloading of HBV DNA virus.