中华肿瘤杂志
中華腫瘤雜誌
중화종류잡지
CHINESE JOURNAL OF ONCOLOGY
2014年
6期
424-429
,共6页
韦腾飞%张军%吴豫%张丹丹%卢龙坤%沈茜
韋騰飛%張軍%吳豫%張丹丹%盧龍坤%瀋茜
위등비%장군%오예%장단단%로룡곤%침천
癌,非小细胞肺%CD4+T淋巴细胞%共抑制分子%免疫逃逸%流式细胞术
癌,非小細胞肺%CD4+T淋巴細胞%共抑製分子%免疫逃逸%流式細胞術
암,비소세포폐%CD4+T림파세포%공억제분자%면역도일%류식세포술
Neoplasm,non-small cell lung%CD4 + T-lymphocytes%Co-inhibitory molecule%Immune escape%Flow cytometry
目的 检测非小细胞肺癌(NSCLC)患者外周血和肿瘤组织中CD4+T细胞表面细胞毒性T淋巴细胞相关抗原4(CTLA-4)、淋巴细胞活化基因3(LAG-3)、程序性死亡分子1(PD-1)和CD39的表达水平,并探讨其与NSCLC疾病进展的关系.方法 选取NSCLC患者53例、疾病对照17例和健康对照18例,共88个研究对象,取新鲜抗凝血,并体外分离13例NSCLC患者肿瘤组织和癌旁组织浸润的淋巴细胞,经流式细胞术检测外周血、肿瘤组织和癌旁组织中CTLA-4、LAG-3、PD-1和CD39共抑制分子的表达.结果 NSCLC患者外周血中CD4+ CTLA-4+T细胞、CD4+ LAG-3+T细胞、CD4+PD-1+T细胞和CD4+ CD39+T细胞的比例分别为(2.49±2.43)％、(2.47 ±3.50)％、(12.94±5.96)％和(6.78±5.21)％,NSCLC患者外周血中CD4+ CTLA-4+T细胞的比例明显高于正常对照组和疾病对照组(P＜0.05),CD4+ PD-1+T细胞的比例也明显高于正常对照组(P＜0.05).进一步分层分析显示,Ⅲ～Ⅳ期NSCLC患者外周血中CD4+ PD-1+T细胞的比例为(13.21±5.96)％,明显高于Ⅰ～Ⅱ期NSCLC患者[(11.06±3.42)％,P＜0.05].NSCLC肿瘤组织中CD4+ CTLA-4+T细胞、CD4+ LAG-3+T细胞和CD4+ PD-1+T细胞的比例分别为(5.07±2.11)％、(7.86±3.24)％和(40.20±18.84)％,均明显高于外周血[(3.13±1.01)％、(2.65±1.48)％和(15.79±5.69)％,均P＜0.05];其中NSCLC肿瘤组织中CD4+ CTLA-4+T细胞和CD4+ PD-1+T细胞的比例还明显高于相应的癌旁组织(均P＜0.05).结论 在NSCLC患者外周血和肿瘤组织中,CD4+T细胞表面共抑制分子CTLA4、LAG-3和PD-1的表达增高,这可能是参与肿瘤细胞免疫逃逸、促进NSCLC疾病进展和预后不良的机制之一.
目的 檢測非小細胞肺癌(NSCLC)患者外週血和腫瘤組織中CD4+T細胞錶麵細胞毒性T淋巴細胞相關抗原4(CTLA-4)、淋巴細胞活化基因3(LAG-3)、程序性死亡分子1(PD-1)和CD39的錶達水平,併探討其與NSCLC疾病進展的關繫.方法 選取NSCLC患者53例、疾病對照17例和健康對照18例,共88箇研究對象,取新鮮抗凝血,併體外分離13例NSCLC患者腫瘤組織和癌徬組織浸潤的淋巴細胞,經流式細胞術檢測外週血、腫瘤組織和癌徬組織中CTLA-4、LAG-3、PD-1和CD39共抑製分子的錶達.結果 NSCLC患者外週血中CD4+ CTLA-4+T細胞、CD4+ LAG-3+T細胞、CD4+PD-1+T細胞和CD4+ CD39+T細胞的比例分彆為(2.49±2.43)％、(2.47 ±3.50)％、(12.94±5.96)％和(6.78±5.21)％,NSCLC患者外週血中CD4+ CTLA-4+T細胞的比例明顯高于正常對照組和疾病對照組(P＜0.05),CD4+ PD-1+T細胞的比例也明顯高于正常對照組(P＜0.05).進一步分層分析顯示,Ⅲ～Ⅳ期NSCLC患者外週血中CD4+ PD-1+T細胞的比例為(13.21±5.96)％,明顯高于Ⅰ～Ⅱ期NSCLC患者[(11.06±3.42)％,P＜0.05].NSCLC腫瘤組織中CD4+ CTLA-4+T細胞、CD4+ LAG-3+T細胞和CD4+ PD-1+T細胞的比例分彆為(5.07±2.11)％、(7.86±3.24)％和(40.20±18.84)％,均明顯高于外週血[(3.13±1.01)％、(2.65±1.48)％和(15.79±5.69)％,均P＜0.05];其中NSCLC腫瘤組織中CD4+ CTLA-4+T細胞和CD4+ PD-1+T細胞的比例還明顯高于相應的癌徬組織(均P＜0.05).結論 在NSCLC患者外週血和腫瘤組織中,CD4+T細胞錶麵共抑製分子CTLA4、LAG-3和PD-1的錶達增高,這可能是參與腫瘤細胞免疫逃逸、促進NSCLC疾病進展和預後不良的機製之一.
목적 검측비소세포폐암(NSCLC)환자외주혈화종류조직중CD4+T세포표면세포독성T림파세포상관항원4(CTLA-4)、림파세포활화기인3(LAG-3)、정서성사망분자1(PD-1)화CD39적표체수평,병탐토기여NSCLC질병진전적관계.방법 선취NSCLC환자53례、질병대조17례화건강대조18례,공88개연구대상,취신선항응혈,병체외분리13례NSCLC환자종류조직화암방조직침윤적림파세포,경류식세포술검측외주혈、종류조직화암방조직중CTLA-4、LAG-3、PD-1화CD39공억제분자적표체.결과 NSCLC환자외주혈중CD4+ CTLA-4+T세포、CD4+ LAG-3+T세포、CD4+PD-1+T세포화CD4+ CD39+T세포적비례분별위(2.49±2.43)％、(2.47 ±3.50)％、(12.94±5.96)％화(6.78±5.21)％,NSCLC환자외주혈중CD4+ CTLA-4+T세포적비례명현고우정상대조조화질병대조조(P＜0.05),CD4+ PD-1+T세포적비례야명현고우정상대조조(P＜0.05).진일보분층분석현시,Ⅲ～Ⅳ기NSCLC환자외주혈중CD4+ PD-1+T세포적비례위(13.21±5.96)％,명현고우Ⅰ～Ⅱ기NSCLC환자[(11.06±3.42)％,P＜0.05].NSCLC종류조직중CD4+ CTLA-4+T세포、CD4+ LAG-3+T세포화CD4+ PD-1+T세포적비례분별위(5.07±2.11)％、(7.86±3.24)％화(40.20±18.84)％,균명현고우외주혈[(3.13±1.01)％、(2.65±1.48)％화(15.79±5.69)％,균P＜0.05];기중NSCLC종류조직중CD4+ CTLA-4+T세포화CD4+ PD-1+T세포적비례환명현고우상응적암방조직(균P＜0.05).결론 재NSCLC환자외주혈화종류조직중,CD4+T세포표면공억제분자CTLA4、LAG-3화PD-1적표체증고,저가능시삼여종류세포면역도일、촉진NSCLC질병진전화예후불량적궤제지일.
Objective To detect the expression levels of co-inhibitory molecules,including CTLA-4,LAG-3,PD-1 and CD39,on CD4 + T cells in peripheral blood or tumor tissues from NSCLC patients and to investigate their potential internal relationships with the progression of NSCLC.Methods Eighty-eight patients including 53 NSCLC,17 disease control cases and 18 healthy controls were studied.All the peripheral blood and 13 cases of tumor and tumor-adjacent tissues from surgically treated NSCLC patients were obtained.The expression levels of co-inhibitory molecules CTLA-4,LAG-3,PD-1 and CD39 were assayed by flow cytometry (FCM).Results The ratios of CD4 + CTLA-4 + T cells,CD4 + LAG-3 + T cells,CD4 + PD-1 + T cells and CD4 + CD39 + T cells in the peripheral blood of NSCLC patients were (2.49 ± 2.43) ％,(2.47 ± 3.50) ％,(12.94 ± 5.96) ％ and (6.78 ± 5.21) ％,respectively,the ratio of CD4 + CTLA-4 + T cells was significantly higher in the peripheral blood of NSCLC patients than that in the disease controls and healthy controls (P ＜ 0.05).The ratio of CD4 + PD-1 + T cells was also highly raised in the peripheral blood of NSCLC patients than that in the healthy controls (P ＜ 0.05).Further stratified analysis indicated that the ratio of CD4 + PD-1 + T cells was (13.21 ± 5.96) ％ in NSCLC patients entering stages Ⅲ and Ⅳ,also significantly increased as compared with that of (11.06 ± 3.42) ％ in the patients undergoing stages Ⅰ and Ⅱ (P＜0.05).More CD4+ CTLA-4+ T cells,CD4+ LAG-3+ T cells and CD4+ PD-1 + T cells were verified in the cancer tissues (5.07 ± 2.11)％,(7.86 ± 3.24)％ and (40.20 ± 18.84)％,respectively,than those in their matched peripheral blood (3.13 ± 1.01) ％,(2.65 ± 1.48) ％ and (15.79 ± 5.69) ％,(P ＜0.05 for all),and especially,CD4 + CTLA-4 + T cells and CD4 + PD-1 + T cells were also highly increased than those in matched cancer-adjacent tissues (P ＜ 0.05 for all).Conclusions The increased expression levels of co-inhibitory molecules CTLA-4,LAG-3 and PD-1 on CD4 + T cells in peripheral blood and tumor tissues may be one of the mechanisms related to immune escape of tumor cells,acceleration of disease progression and poor prognosis in NSCLC patients.
