垂体腺瘤患者外周血淋巴细胞亚群的分布及其临床意义

The distribution of peripheral blood lymphocyte subsets and its clinical significance in patients with pituitary adenomas

目的探讨不同类型垂体腺瘤患者的外周血T淋巴细胞亚群分布情况、自然杀伤(NK)细胞的活性及其临床意义。方法前瞻性纳入2010年3月至2016年10月苏州大学附属第一医院神经外科收治的垂体腺瘤患者,共215例,同期纳入95名健康体检者作为健康对照组(简称对照组)。采用流式细胞术检测不同分型的垂体腺瘤患者及对照组外周血中的CD3^(+)、CD3^(+)CD4^(+)、CD3^(+)CD8^(+)、CD3^(+)CD25^(+)、CD3^(+)CD69^(+)、CD3^(+)HLA^(-)DR^(+)、CD3-HLA^(-)DR^(+)和CD3-CD(16^(+)56)^(+)(即NK)淋巴细胞的占比并进行组间比较,同时探讨垂体腺瘤患者不同淋巴细胞亚群的占比与其临床特征的关系。结果在总体垂体腺瘤组(215例)中,外周血中的CD3^(+)细胞占比较对照组降低,而CD3^(+)CD25^(+)、CD3^(+)HLA^(-)DR^(+)细胞占比均较对照组升高,差异均有统计学意义(均P<0.05)。与对照组比较,(1)无功能腺瘤患者外周血中CD3^(+)细胞的占比降低,而CD3^(+)CD25^(+)和CD3^(+)HLA^(-)DR^(+)细胞的占比升高(均P<0.05);(2)生长激素(GH)腺瘤和催乳素(PRL)腺瘤患者的CD3^(+)CD8^(+)、CD3^(+)CD25^(+)及CD3^(+)HLA^(-)DR^(+)细胞的占比均升高,而NK细胞的占比下降(均P<0.05);(3)促肾上腺皮质激素(ACTH)腺瘤患者的CD3^(+)CD4^(+)细胞、NK细胞的占比均下降,而CD3^(+)CD8^(+)、CD3^(+)CD25^(+)、CD3^(+)CD69^(+)及CD3^(+)HLA^(-)DR^(+)细胞的占比均升高(均P<0.05)。基于2017版垂体腺瘤分类标准分型的GH细胞腺瘤、促性腺激素细胞腺瘤、裸细胞腺瘤患者外周血中CD3^(+)细胞的占比均较对照组下降(均P<0.05);GH细胞腺瘤、ACTH细胞腺瘤、多激素和双激素细胞腺瘤患者的NK细胞占比均较对照组降低(均P<0.05);GH细胞腺瘤、PRL细胞腺瘤、ACTH细胞腺瘤、促性腺激素细胞腺瘤、裸细胞腺瘤、多激素和双激素细胞腺瘤患者的CD3^(+)CD25^(+)及CD3^(+)HLA^(-)DR^(+)细胞占比均较对照组升高(均P<0.05)。在PRL细胞腺瘤、多激素和双激素细胞腺瘤组中,CD3-HLA^(-)DR^(+)细胞占比较对照组降低(P<0.05)。垂体巨腺瘤组(肿瘤最大径>4 cm)患者CD3^(+)细胞的占比低于大腺瘤组(1~4 cm)和微腺瘤组(<1 cm)(均P<0.05)。与非侵袭组相比,侵袭组CD3^(+)细胞的占比降低,而CD3^(+)CD25^(+)细胞的占比升高(均P<0.05);复发性垂体腺瘤患者的NK细胞占比低于原发性垂体腺瘤患者(P<0.05)。结论不同类型的垂体腺瘤患者均存在免疫功能的改变,主要表现为细胞免疫或NK细胞的免疫抑制作用;垂体腺瘤患者免疫功能的抑制可能与肿瘤的负荷、侵袭性以及是否为复发性肿瘤有关。

Objective To investigate the distribution of T-lymphocyte subsets and natural killer(NK)cells activity in peripheral blood from patients with pituitary adenomas and its clinical significance.Methods A total of 215 patients with pituitary adenomas who were admitted to Department of Neurosurgery,the First Affiliated Hospital of Soochow University from March 2010 to October 2016 were prospectively enrolled in this study.In the same period,95 healthy subjects were included as the healthy control group(referred to as the control group).Flow cytometry was used to detect the proportions of CD3^(+),CD3^(+)CD4^(+),CD3^(+)CD8^(+),CD3^(+)CD25^(+),CD3^(+)CD69^(+),CD3^(+)HLA^(-)DR^(+),CD3-HLA^(-)DR^(+)and CD3-CD(16^(+)56)^(+)(NK)cells in the peripheral blood of patients with different types of pituitary adenomas and the control group,which were compared between groups.The relationship between different proportions of lymphocyte subsets and clinical characteristics of patients with pituitary adenomas was explored.Results In the pituitary adenoma group(215 cases),the proportion of CD3^(+)cells in peripheral blood was lower than that in the control group,while CD3^(+)CD25^(+)and CD3^(+)HLA^(-)DR^(+)cells were higher than the control group,and the differences were statistically significant(all P<0.05).Compared with the control group,(1)the proportion of CD3^(+)cells in peripheral blood of patients with non-functioning adenoma decreased,while the proportion of CD3^(+)CD25^(+)and CD3^(+)HLA^(-)DR^(+)cells increased(all P<0.05);(2)in the growth hormone(GH)adenoma and prolactin(PRL)adenoma patients,the proportions of CD3^(+)CD8^(+),CD3^(+)CD25^(+)and CD3^(+)HLA^(-)DR^(+)cells increased,while the proportion of NK cells decreased(all P<0.05);(3)in patients with adrenocorticotropic hormone(ACTH)adenomas,the proportions of CD3^(+)CD4^(+)cells and NK cells decreased,while the proportions of CD3^(+)CD8^(+),CD3^(+)CD25^(+),CD3^(+)CD69^(+)and CD3^(+)HLA^(-)DR^(+)cells increased(all P<0.05).The proportion of CD3^(+)cells in the peripheral blood of patients with GH cell adenoma,gonadotropin cell adenoma,and naked cell adenoma(based on the 2017 WHO Classification of Pituitary Adenoma)was lower than that of the control group(all P<0.05).The proportion of NK cells in patients with GH cell adenoma,ACTH cell adenoma,multihormonal and dual hormone cell adenoma was lower than that of the control group(all P<0.05).The proportions of CD3^(+)CD25^(+)and CD3^(+)HLA^(-)DR^(+)cells in patients with GH cell adenoma,ACTH cell adenoma,PRL cell adenoma,gonadotropin cell adenoma,naked cell adenoma,multihormonal and dual hormone cell adenomas were higher than those in the control group(all P<0.05).In the PRL cell adenoma,multihormonal and dual hormone cell adenoma groups,the proportion of CD3-HLA^(-)DR^(+)cells was lower than that of the control group(P<0.05).The proportion of CD3^(+)cells in the giant pituitary adenoma group(tumor diameter>4 cm)was lower than that in the large adenoma group(1-4 cm)and microadenoma group(<1 cm)(both P<0.05).Compared with the non-invasive group,the proportion of CD3^(+)cells in the invasion group decreased,while the proportion of CD3^(+)CD25^(+)cells increased(both P<0.05).The proportion of NK cells in patients with recurrent pituitary adenoma was lower than that in patients with primary pituitary adenoma(P<0.05).Conclusions Patients with different types of pituitary adenomas have changes in immune function,which are mainly manifested as the function suppression of cellular immunity or NK cell.The suppression of immune function in patients with pituitary adenomas may be related to tumor burden,tumor invasiveness and recurrence.