Dynamic Immune Function Changes Before And After The First Radioactive Iodine Therapy After Total Resection Of Differentiated Thyroid Carcinoma

Purpose:It is well known that immunity plays a crucial role in the occurrence and development of tumors.However,little is known about the effects of total thyroidectomy and radioactive iodine therapy(RAIT)on circulating lymphocyte subsets in DTC patients.The present study aimed to investigate the changes of circulating lymphocyte subsets in DTC patients after total thyroidectomy and dynamic changes of them before and after RAIT.Methods:A total of 105 participants were enrolled in the study,including 45 patients with DTC and 60 healthy controls(HC)with age and gender matched.All patients were treated with total thyroidectomy and RAIT according to the EANM guidelines.Thyroid and immune function tests were evaluated at 0,30 and 90 days after RAIT.Circulating lymphocyte subsets were detected by modified flow cytometry.In addition,the correlation analysis of lymphocyte subsets and Tg levels in DTC patients was performed to evaluate its clinical significance.Results:1.The percentage(3.8±0.6)and absolute count(25.3±8.9)of Tregs in peripheral blood of DTC patients after total thyroidectomy were significantly lower than those of HC(4.7±1.4,P<0.001;32.1±11.7,P=0.002).The percentage of circulating Th17 cells in DTC patients(1.3±0.3)was significantly higher than that in HC(1.1±0.5,P=0.027),but the absolute count(9.2±3.9)and HC(8.1±4.5,P=0.172)had no significant change.2.Compared with patients without lymph node metastasis(214.7±92.3),the absolute count of Th1 cells in the blood circulation of DTC patients with lymph node metastasis(148.3±71.8,P=0.037)was significantly reduced.The absolute count of peripheral blood B(270.6±126.9)and NK cells were significantly increased(311.7±124.9)in patients with tumor size>1cm compared with patients with tumor size≤1cm(202.1±81.8,P=0.038;234.7±116.2,P=0.038).The absolute count of Th17(10.4±4.2)and CD4~+T cells(716.2±212.6)in peripheral blood of patients with multiple lesions were significantly higher than those of patients with single lesions(7.5±2.7,P=0.014;577.2±171.5,P=0.026).The absolute count of CD8~+T cells in peripheral blood of patients with peripheral tissue infiltration after DTC surgery was significantly lower(471.7±145.1)than that of patients without peripheral tissue infiltration(627.9±298.4,P=0.02).Compared with female patients(243.8±89.3),the absolute count of NK cells in the peripheral blood of male patients was significantly higher(319.5±158.0,P=0.046).Age and whether the disease was confined to one side had no significant effect on the immune status of peripheral blood(P>0.05).3.Compared with before RAIT,the total T(1011.4±290.8),total B(96.1±52.1),CD4~+T(497.5±194.2)and CD8~+T absolute count(470.7±190.9)decreased significantly 30 days after RAIT(both P<0.05).The absolute count of NK cells(292.2±133.1)had no significant change compared with that before RAIT(274.1±125.6,P=0.230).Compared with the 30th day after RAIT,the total T(1140.5±285.3),total B(149.1±92.3),CD4~+T(561.6±162.4)and CD8~+T absolute count(523.1±203.7)gradually recovered after RAIT(both P<0.05),but most lymphocyte subsets(total T,total B,and CD4~+T)had not recovered to pre-RAIT levels(both P<0.05).In terms of CD4~+T cell subsets,Th1(122.5±68.7),Th2(5.7±2.7),Th17(6.9±3.5)and Tregs absolute count(20.4±10.7)decreased significantly on the 30th day after RAIT compared with those before RAIT(both P<0.05).On the 90th day,only the absolute count of Tregs(22.9±8.3)increased significantly compared with the 30th day(20.4±10.7,P=0.027),and returned to the level before iodine therapy(25.3±8.9,P>0.05).The absolute count of Th2 cells(6.6±5.5)was not significantly different from that on day 30(5.7±2.7,P=0.232).However,we found no significant difference in absolute Th2 cell count on day 90 after RAIT compared with pre-RAIT(7.3±2.9,P=0.481),suggesting a recovery in circulating Th2 cell levels.4.Comparative analysis of the ratio of circulating lymphocyte subsets showed that after total thyroidectomy in DTC patients,Th1/Tregs(6.3±2.6),Th2/Tregs(0.3±0.1),Th17/Tregs(0.3±0.11)and B/Tregs ratio(10.1±5.8)was significantly different from HC(both P<0.05).After RAIT treatment,Th1/Tregs(4.8±2.7),Th2/Tregs(0.3±0.2),Th17/Tregs Tregs(0.3±0.08)and B/Tregs ratio(7.0±4.6)returned to normal levels(both P<0.05).5.This study found that the percentage of Th17 cells before RAIT in DTC patients was significantly positively correlated with thyroglobulin(Tg)levels at days 30 and 90after RAIT(both P<0.05).Conclusions:1.The absolute count of circulating Tregs in DTC patients after total thyroidectomy were significantly decreased,while the absolute count of Th17 cells remained unchanged,suggesting that Tregs play a crucial role in tumor immune tolerance.2.Lymphoid metastases,tumor volume,number of lesions,surrounding tissue infiltration,and gender differences may contribute to changes in absolute count of different lymphocyte subsets.3.Absolute count of multiple lymphocyte subsets decreased in DTC patients in the short term after RAIT,and these cells recovered rapidly over time.4.The balance of lymphocyte subsets in DTC patients after total thyroidectomy is disordered,and some immune balances return to normal levels after RAIT.5.The percentage of Th17 cells before RAIT may be an important predictor of poor prognosis in patients with DTC.