CAJ | 학술논문

目的:研究晚期卵巢癌患者经一线化疗后体内CD8+T细胞和NK细胞数量及功能的动态变化.方法:选取术后行紫杉醇联合卡铂化疗的晚期卵巢上皮癌患者共13例,采集化疗前(S_0)、化疗后5-7天(S_1)、化疗后12～14天(S_2)和化疗后25～28天(S_3)外周血,流式细胞术检测患者外周血中CD3~+、CD4~+、CD8~+和NK细胞的百分比及绝对数量.采用体外自体肿瘤细胞裂解物脉冲淋巴细胞共培养的方法检测不同时间点CD8~+T细胞IFN-γ的分泌功能,并以LDH释放法测定NK细胞对K562细胞的杀伤活性.结果:在一个完整的化疗周期中,CD3~+、CD4~+、CD8~+细胞的绝对数目均于S_1期降至最低点,且与S_0期分别都有显著性差异.与对照组相比,当体外给予自身肿瘤细胞裂解物刺激诱导培养后,在S_1、S_2和S_3期产生IFN-γ的CD8~+细胞比例均较对照组显著增加,且CD8~+IFN-γ~+细胞比例在S2期达到最高.NK细胞的绝对数目于S1期降至最低点,且与S0期有显著性差异,NK细胞的比例及杀伤活性在化疗前、后均无显著性差异.结论:卵巢癌患者于一线化疗后机体经历免疫重建的过程,该过程中CD8~+T细胞介导的免疫应答一过性增高,而NK细胞的杀伤活性无明显变化.化疗后免疫重建期可能是免疫治疗实施的最佳窗口期.
목적:연구만기란소암환자경일선화료후체내CD8+T세포화NK세포수량급공능적동태변화.방법:선취술후행자삼순연합잡박화료적만기란소상피암환자공13례,채집화료전(S_0)、화료후5-7천(S_1)、화료후12～14천(S_2)화화료후25～28천(S_3)외주혈,류식세포술검측환자외주혈중CD3~+、CD4~+、CD8~+화NK세포적백분비급절대수량.채용체외자체종류세포렬해물맥충림파세포공배양적방법검측불동시간점CD8~+T세포IFN-γ적분비공능,병이LDH석방법측정NK세포대K562세포적살상활성.결과:재일개완정적화료주기중,CD3~+、CD4~+、CD8~+세포적절대수목균우S_1기강지최저점,차여S_0기분별도유현저성차이.여대조조상비,당체외급여자신종류세포렬해물자격유도배양후,재S_1、S_2화S_3기산생IFN-γ적CD8~+세포비례균교대조조현저증가,차CD8~+IFN-γ~+세포비례재S2기체도최고.NK세포적절대수목우S1기강지최저점,차여S0기유현저성차이,NK세포적비례급살상활성재화료전、후균무현저성차이.결론:란소암환자우일선화료후궤체경력면역중건적과정,해과정중CD8~+T세포개도적면역응답일과성증고,이NK세포적살상활성무명현변화.화료후면역중건기가능시면역치료실시적최가창구기.
Objective: The purpose of this study is to investigate the dynamic changes in the numbers and functions of CD8~+T cells and NK cells in patients with advanced ovarian cancer undergoing first line chemotherapy,so as to identify whether there was a "window period" of anti-tumor immune suppression reverse after chemotherapy.Methods: Peripheral blood samples from each ovarian cancer patient were obtained before (S_0) and at day 5-7 (S_1),day 12-14 (S_2) and day 25-28 (S_3) after Chemotherapy in 13 patients.The numbers and proportions of CD3~+,CD4~+,CD8~+ and nature killer (NK) cells were analyzed by flow cytometry technique.The percentages of specific IFN-γ-secreting CD8~+ cells were also calculated after that peripheral lymphocytes had been stimulated with self tumor lysates.Cytotoxicity of NK cells against K562 cells was detected by LDH releasing assay.Results: The numbers of CD3~+,CD4~+,CD8~+T cells and NK cells reduced to the lowest on S1.Compared to those of the control group,and the percentages of IFN-γ-secreting CD8~+T cells were remarkably higher on S_1,S_2 and S_3 when CD8~+T cells were stimulated with autologous tumor antigen,and the percentage of CD8~+IFN-γ~+ cell reached the highest on S2.No significant differences of NK cell cytotoxicity against K562 cells were found on S_1,S_2 and S_3 compared to S0.Conclusion: Paclitaxel and carboplatin induce lymphopenia,which triggers the temporary immune reconstitution.During immune reconstitution the enhanced priming of CD8~+T cell response by autologons tumor antigen is found while the function of NK cells does not change significantly.It probably turns out that the" window period"during immune reconstitution offers a best opportunity for cancer immunotherapy.