结直肠癌及腺瘤患者CD4~+、CD8~+和CD28~+T淋巴细胞的亚群变化及临床意义
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摘要
背景与目的:结直肠癌(colorectal cancer,CRC)严重影响患者生存。探讨肿瘤微环境(tumor microenvironment,TME)T细胞亚群在CRC和腺瘤中的表达及意义。方法:用免疫组织化学法和流式细胞术对51例健康人(对照组)、46例结直肠腺瘤(腺瘤组)、100例CRC(癌症组)和15例CRC术后(癌术后组)患者进行T细胞亚群检测。结果:(1)对照组、腺瘤组及癌症组3组中CD4~+T细胞的阳性率分别是90.00%、43.75%及32.65%,CD8~+T淋巴细胞的阳性率分别是30.00%、56.25%及75.51%,CD28~+T淋巴细胞的阳性率分别是42.86%、30.00%及20.00%。(2)对照组、腺瘤组及癌症组3组中CD4~+、CD4~+/CD8~+、CD28~+、CD8~+CD28~+和CD8~-CD28~+逐渐降低,CD8~+、CD8~+CD28-逐渐增加(P<0.05);癌术前术后T细胞亚群差异有统计学意义(P<0.05)。结论:(1)CRC微环境T细胞亚群中CD4~+、CD4~+/CD8~+、CD28~+、CD8~+CD28~+和CD8~-CD28~+呈递减趋势,CD8~+、CD8~+CD28~-呈递增趋势,且在癌前病变腺瘤中已逐步出现上述趋势变化。(2)CRC患者行肿瘤切除术后,其T细胞亚群有所恢复,故在一定程度上,CRC中T细胞亚群的变化可以早期预测结直肠疾病的发展。
Background and purpose: Colorectal cancer(CRC) is a disease that seriously affects the quality of life. This study aimed to investigate the subsets and significance of tumor cell microenvironment T cell in CRC and adenoma. Methods: Immunohistochemistry and flow cytometry were used to test T lymphocyte subsets in 51 healthy subjects(control group), 46 patients with colorectal adenomas(adenoma group), 100 CRC patients(cancer group), and 15 postoperative patients with CRC(postoperative group). Results: The positive rates of CD4~+ T cells in the control group, adenoma group and cancer group were 90.00%, 43.75% and 32.65%, respectively. The positive rates of CD8~+T lymphocytes were 30.00%, 56.25% and 75.51%, respectively. The positive rates of CD28~+ T lymphocytes were 42.86%, 30.00% and 20.00%, respectively. The levels of CD4~+, CD4~+/CD8~+, CD28~+, CD8~+CD28~+ and CD8~-CD28~+in the control group, adenoma group and cancer group gradually decreased, while the CD8~+ and CD8~+CD28~-levels gradually increased(P<0.05). The difference in T cell subsets between preoperative and postoperative patients was statistically significant(P<0.05). Conclusion: CD4~+, CD4~+/CD8~+, CD28~+, CD8~+CD28~+ and CD8~-CD28~+ in the subgroup of colorectal tumor microenvironment showed a declining trend, while CD8~+ and CD8~+CD28~-showed an increasing trend. Moreover, these trends gradually appeared in precancerous adenomas. After CRC patients underwent tumor resection, their T cell subsets recovered. Therefore, to some extent, the changes of T cell subsets in CRC can predict the development of colorectal disease early.
Background and purpose: Colorectal cancer(CRC) is a disease that seriously affects the quality of life. This study aimed to investigate the subsets and significance of tumor cell microenvironment T cell in CRC and adenoma. Methods: Immunohistochemistry and flow cytometry were used to test T lymphocyte subsets in 51 healthy subjects(control group), 46 patients with colorectal adenomas(adenoma group), 100 CRC patients(cancer group), and 15 postoperative patients with CRC(postoperative group). Results: The positive rates of CD4~+ T cells in the control group, adenoma group and cancer group were 90.00%, 43.75% and 32.65%, respectively. The positive rates of CD8~+T lymphocytes were 30.00%, 56.25% and 75.51%, respectively. The positive rates of CD28~+ T lymphocytes were 42.86%, 30.00% and 20.00%, respectively. The levels of CD4~+, CD4~+/CD8~+, CD28~+, CD8~+CD28~+ and CD8~-CD28~+in the control group, adenoma group and cancer group gradually decreased, while the CD8~+ and CD8~+CD28~-levels gradually increased(P<0.05). The difference in T cell subsets between preoperative and postoperative patients was statistically significant(P<0.05). Conclusion: CD4~+, CD4~+/CD8~+, CD28~+, CD8~+CD28~+ and CD8~-CD28~+ in the subgroup of colorectal tumor microenvironment showed a declining trend, while CD8~+ and CD8~+CD28~-showed an increasing trend. Moreover, these trends gradually appeared in precancerous adenomas. After CRC patients underwent tumor resection, their T cell subsets recovered. Therefore, to some extent, the changes of T cell subsets in CRC can predict the development of colorectal disease early.
引文
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[19]王桂玲.胃癌患者肿瘤浸润淋巴细胞CD28表达的检测及临床意义研究[J].现代诊断与治疗,2017,28(17):3297-3298.
[20]余铭,陈积贤,施正超,等.大肠癌患者外周血CD8和CD28检测的临床意义[J].中国医师进修杂志,2009,32(35):10-12.
[21]王仲,周新伏,唐铁钢,等.热化疗对晚期恶性肿瘤患者外周血CD8+CD28+T细胞表达的影响及临床意义[J].肿瘤防治研究,2011,38(12):1405-1408.
[22]STRIOGA M,PASUKONIENE V,CHARACIEJUS D,et al.CD8+CD28-and CD8+CD57+T cells and their role in health and disease[J].Immunology,2011,134(1):17-32.
[23]XU W,LIU H,SONG J,et al.The appearance of Tregs in cancer nest is a promising independent risk factor in colon cancer[J].J Cancer Res Clin Oncol,2013,139(11):1845-1852.
[24]LING A,EDIN S,WIKBERG M L,et al.The intratumoural subsite and relation of CD8(+)and FOXP3(+)T lymphocytes in colorectal cancer provide important prognostic clues[J].Br J Cancer,2014,110(10):2551-2559.
[2]袁龙,黄涛,徐本玲,等.程序性死亡分子-1+T细胞免疫球蛋白黏蛋白结构域相关分子-3+细胞在结直肠癌患者外周血及组织CD4+T淋巴细胞中的比例及临床意义[J].中华实验外科杂志,2017,34(5):856-859.
[3]王海波,刘海义,苏文,等.直肠癌新辅助治疗后外周血调节性T细胞水平与肿瘤缓解的关系[J].中华胃肠外科杂志,2015,18(4):361-364.
[4]彭秀娟,马永能,刘国雄,等.HIV感染者CD4+T细胞数与IL-10、TNF-α表达水平的相关性[J].国际检验医学杂志,2016,37(8):1081-1082.
[5]BUHRMANN C,KRAEHE P,LUEDERS C,et al.Curcumin suppresses crosstalk between colon cancer stem cells and stromal fibroblasts in the tumor microenvironment:potential role of EMT[J].Plo S One,2014,9(9):e107514.
[6]SCHARPING N E,MENK A V,MORECI R S,et al.The tumor microenvironment represses T cell mitochondrial biogenesis to drive intratumoral T cell metabolic insufficiency and dysfunction[J].Immunity,2016,45(2):374-388.
[7]周蕾,姜妮,王小利,等.中晚期胃癌患者外周血T细胞亚群检测的临床意义[J].中国肿瘤临床,2017,44(5):224-227.
[8]MKRTICHYAN M,NAJJAR Y G,RAULFS E C,et al.B7-DCIg enhances vaccine effect by a novel mechanism dependent on PD-1 expression level on T cell subsets[J].J Immunol,2012,189(5):2338-2247.
[9]SONG Q K,REN J,ZHOU X N,et al.The prognostic value of peripheral CD4+CD25+T lymphocytes among early stage and triple negative breast cancer patients receiving dendritic cellscytokine induced killer cells infusion[J].Oncotarget,2015,6(38):41350-41359.
[10]OSI?SKA I,STELMASZCZYK-EMMEL A,POLUBIECKOWNACKA M et al.CD4+/CD25(high)/Fox P3+/CD127-regulatory T cells in bronchoalveolar lavage fluid of lung cancer patients[J].Hum Immunol,2016,77(10):912-915.
[11]刘晓光,金秀国,刘波,等.结肠癌患者外周血淋巴细胞CD8和CD28的表达[J].肿瘤学杂志,2007,13(1):68-69.
[12]李波.结直肠癌患者外周血中淋巴细胞亚群的改变[J].全科医学临床与教育,2016,14(5):503-505.
[13]TANNER S M,DAFT J G,HILL S A,et al.Altered T-cell balance in lymphoid organs of a mouse model of colorectal cancer[J].J Histochem Cytochem,2016,64(12):753-767.
[14]YU W,WANG Y,GUO P.Notch signaling pathway dampens tumor-infiltrating CD8+T cells activity in patients with colorectal carcinoma[J].Biomed Pharma cother,2018,97:535-542.
[15]王嘉,曲秀娟,张敬东,等.肠癌患者外周血T淋巴细胞亚群数量及临床意义[J].中国医科大学学报,2014,43(4):289-292.
[16]HADRUP S,DONIA M,THORSTRATEN P.Effector CD4 and CD8 T cells and their role in the tumor microenvironment[J].Cancer Microenviron,2013,6(2):123-133.
[17]刘畅,王红艳.CD8+T细胞活化与分化的分子机制[J].中国免疫学杂志,2017,33(4):481-487.
[18]陈耀平,屈蕾,陈静,等.胃癌患者外周血CD8+CD28+与CD8+CD57+T细胞亚群的变化及临床意义[J].宁夏医科大学学报,2017,39(9):1003-1005,1011.
[19]王桂玲.胃癌患者肿瘤浸润淋巴细胞CD28表达的检测及临床意义研究[J].现代诊断与治疗,2017,28(17):3297-3298.
[20]余铭,陈积贤,施正超,等.大肠癌患者外周血CD8和CD28检测的临床意义[J].中国医师进修杂志,2009,32(35):10-12.
[21]王仲,周新伏,唐铁钢,等.热化疗对晚期恶性肿瘤患者外周血CD8+CD28+T细胞表达的影响及临床意义[J].肿瘤防治研究,2011,38(12):1405-1408.
[22]STRIOGA M,PASUKONIENE V,CHARACIEJUS D,et al.CD8+CD28-and CD8+CD57+T cells and their role in health and disease[J].Immunology,2011,134(1):17-32.
[23]XU W,LIU H,SONG J,et al.The appearance of Tregs in cancer nest is a promising independent risk factor in colon cancer[J].J Cancer Res Clin Oncol,2013,139(11):1845-1852.
[24]LING A,EDIN S,WIKBERG M L,et al.The intratumoural subsite and relation of CD8(+)and FOXP3(+)T lymphocytes in colorectal cancer provide important prognostic clues[J].Br J Cancer,2014,110(10):2551-2559.
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