结肠癌galectin-3蛋白的表达与微环境Foxp3+、IL-17+淋巴细胞的相关性
Correlation between Galectin-3 Protein and Foxp3+, IL-17+ Lymphocytes in Colon Cancer Microenvironment

作者: 李昌宾 , 黄志良 , 李楠 , 刘海鹰 :广州医科大学附属肿瘤医院,胃肠肿瘤外科,广东 广州;

关键词: 结肠肿瘤相关性免疫微环境半乳糖凝素白介素-17Colon Cancer Correlation Immune Microenvironment Galectin Interleukin-17

摘要:
背景:Galectin-3(gal-3)参与多种肿瘤的发生、发展,并可调控免疫细胞的活性。肿瘤微环境中Th17细胞和调节性T细胞(Treg)可影响肿瘤的发展和归转。目前关于结肠癌gal-3蛋白与微环境免疫细胞的关系研究尚少,因此本研究拟分析肿瘤gal-3的表达与微环境Foxp3+、IL-17A+淋巴细胞的相关性,为深入了解结肠癌相关蛋白对免疫微环境的作用提供基础。方法:收集2011-2012年在广州医科大学附属肿瘤医院进行手术切除的结肠癌组织50例和10例对照正常组织,通过免疫组化技术检测组织中gal-3、IL-17A、Foxp3的表达情况,结合临床病理参数分析三者间的表达意义和相关性。结果:Gal-3蛋白主要表达于肿瘤细胞的胞浆,Foxp3蛋白主要表达在间质组织淋巴细胞的胞核中,IL-17A见于间质淋巴细胞的胞浆。结果显示肿瘤组织和间质中的gal-3、Foxp3和IL-17A阳性表达率均显著高于正常结肠上皮组织。其中gal-3在中晚期结肠癌中表达水平明显高于早期病例,而Foxp3+、IL-17A+淋巴细胞比例在中晚期病例中也显著升高。相关性分析显示,肿瘤组织的gal-3表达水平与肿瘤间质中Foxp3+细胞和IL-17A+细胞的阳性比例呈正相关(r = 0.608,P < 0.001;r = 0.289,P = 0.042),即肿瘤细胞表达gal-3越高,间质组织中浸润的Fopx3+细胞和IL-17A+细胞越多。结论:Gal-3蛋白可能促进微环境中Foxp3+、IL-17A+淋巴细胞的浸润参与结肠癌的生长和进展。

Abstract: Background: Galectin-3 (gal-3) involves in tumor development, progression, and regulates im-mune cells activity. Th17 cells and T regulatory cells (Treg) in tumor environment could affect tumor progression and prognosis. Recently few researches investigated the relation between gal-3 and immune cells in colon cancer microenvironment, therefore this research aimed to demonstrate the correlation between gal-3 and Foxp3+, IL-17A+ lymphocytes in colon cancer microenvironment, for further investigating the effect on immune microenvironment from colon cancer- associated protein. Methods: From 2011 to 2012, fifty colon cancer tissue samples and 10 adjacent normal tissues after resection in Affiliated Cancer Hospital of Guangzhou Medical University were collected. Expressions of gal-3, IL-17A and Foxp3 were detected by using immuno histochemistry (IHC) technique. Correlation and significance among these three markers were analyzed with clinical-pathological data. Results: Gal-3 was mainly expressed in cytoplasm of tumor cells, Foxp3 was often found in cellular nuclear of stroma lymphocytes, and IL-17A was expressed in cytoplasm of stroma lymphocytes. Analysis showed the positive expressions of gal-3, Foxp3 and IL-17A were all significantly higher than in normal colon tissues. Expressions of gal-3 in late stage cases were much higher than in early cases, as well as the Foxp3+ lymphocytes and IL-17A+ lymphocytes. Univariate analysis revealed stroma infiltrating Foxp3+ lymphocytes and IL-17A+ lymphocytes had positive correlation with tumoral gal-3 expression (r = 0.608, P < 0.001, r = 0.289, P = 0.042), which means the higher expression of gal-3 in tumor was, the more stroma infiltrating Foxp3+ lymphocytes and IL-17A+ lymphocytes were. Conclusion: Gal-3 might promote Foxp3+ lymphocytes and IL-17A+ lymphocytes infiltration in tumor microenvironment and involve in colon cancer growth and development.

文章引用: 李昌宾 , 黄志良 , 李楠 , 刘海鹰 (2017) 结肠癌galectin-3蛋白的表达与微环境Foxp3+、IL-17+淋巴细胞的相关性。 世界肿瘤研究, 7, 32-39. doi: 10.12677/WJCR.2017.72006

参考文献

[1] 陈万青, 张思维, 曾红梅, 等. 中国2010年恶性肿瘤发病与死亡[J]. 中国肿瘤, 2014, 23(1): 1-10.

[2] Whiteside, T.L. (2008) The Tumor Microenvironment and Its Role in Promoting Tumor Growth. Oncogene, 27, 5904-5912.
https://doi.org/10.1038/onc.2008.271

[3] Chen, J., Jiang, C.C., Jin, L. and Zhang, X.D. (2016) Regulation of PD-L1: A Novel Role of Pro-Survival Signalling in Cancer. Annals of Oncology, 27, 409-416.
https://doi.org/10.1093/annonc/mdv615

[4] Sanjuan, X., Fernandez, P.L., Castells, A., et al. (1997) Differential Expression of Galectin 3 and Galectin 1 in Colorectal Cancer Progression. Gastroenterology, 113, 1906-1915.
https://doi.org/10.1016/S0016-5085(97)70010-6

[5] Leffler, H., Carlsson, S., Hedlund, M., et al. (2004) Introduction to Galectins. Glycoconjugate Journal, 19, 433-440.
https://doi.org/10.1023/B:GLYC.0000014072.34840.04

[6] Califice, S., Castronovo, V. and Van Den Brule, F. (2004) Galectin-3 and Cancer (Review). International Journal of Oncology, 25, 983-992.

[7] Tsuboi, K., Shimura, T., Masuda, N., et al. (2007) Galectin-3 Expression in Colorectal Cancer: Relation to Invasion and Metastasis. Anticancer Research, 27, 2289-2296.

[8] Nishikawa, H. and Sakaguchi, S. (2010) Regulatory T cells in Tumor Immunity. International Journal of Cancer, 127, 759-767.
https://doi.org/10.1002/ijc.25429

[9] Ma, G.F., Miao, Q., Liu, Y.M., et al. (2014) High FoxP3 Expression in Tumour Cells Predicts Better Survival in Gastric Cancer and Its Role in Tumour Microenvironment. British Journal of Cancer, 110, 1552-1560.
https://doi.org/10.1038/bjc.2014.47

[10] Gallimore, A.M. and Simon, A.K. (2008) Positive and Negative Influences of Regulatory T cells on Tumour Immunity. Oncogene, 27, 5886-5893.
https://doi.org/10.1038/onc.2008.269

[11] Tosolini, M., Kirilovsky, A., Mlecnik, B., et al. (2011) Clinical Impact of Different Classes of Infiltrating T Cytotoxic and Helper cells (Th1, Th2, Treg, Th17) in Patients with Colorectal Cancer. Cancer Res, 71, 1263-1271.
https://doi.org/10.1158/0008-5472.CAN-10-2907

[12] Wu, S., Rhee, K.J., Albesiano, E., et al. (2009) A Human Colonic Commensal Promotes Colon Tumorigenesis via Activation of T Helper Type 17 T Cell Responses. Nature Medicine, 15, 1016-1022.
https://doi.org/10.1038/nm.2015

[13] Amicarella, F., Muraro, M.G., Hirt, C., et al. (2017) Dual Role of Tumour-Infiltrating T Helper 17 Cells in Human Colorectal Cancer. Gut, 66, 692-704.
https://doi.org/10.1136/gutjnl-2015-310016

[14] Benchetrit, F., Ciree, A., Vives, V., et al. (2002) Interleukin-17 Inhibits Tumor Cell Growth by Means of a T-Cell-Dependent Mechanism. Blood, 99, 2114-2121.

[15] Murugaiyan, G. and Saha, B. (2009) Protumor vs Antitumor Functions of IL-17. The Journal of Immunology, 183, 4169-4175.
https://doi.org/10.4049/jimmunol.0901017

[16] Fontenot, J.D., Gavin, M.A. and Rudensky, A.Y. (2003) Foxp3 Programs the Development and Function of CD4+CD25+ Regulatory T Cells. Nature Immunology, 4, 330-336.
https://doi.org/10.1038/ni904

[17] Huynh, A., Zhang, R. and Turka, L.A. (2014) Signals and Pathways Controlling Regulatory T Cells. Immunological Reviews, 258, 117-131.
https://doi.org/10.1111/imr.12148

[18] Hori, S., Nomura, T. and Sakaguchi, S. (2003) Control of Regulatory T Cell Development by the Transcription Factor Foxp3. Science, 299, 1057-1061.
https://doi.org/10.1126/science.1079490

[19] Kendal, A.R., Chen, Y., Regateiro, F.S., et al. (2011) Sustained Suppression by Foxp3+ Regulatory T Cells Is Vital for Infectious Transplantation Tolerance. The Journal of Experimental Medicine, 208, 2043-2053.
https://doi.org/10.1084/jem.20110767

[20] Taflin, C., Nochy, D., Hill, G., et al. (2010) Regulatory T Cells in Kidney Allograft Infiltrates Correlate with Initial Inflammation and Graft Function. Transplantation, 89, 194-199.
https://doi.org/10.1097/TP.0b013e3181c3ca11

分享
Top