|本期目录/Table of Contents|

[1]李美,来佳丹,魏诗瑶,等.肾透明细胞癌来源的IL4I1介导PD1+CD8+ T淋巴细胞募集的相关研究[J].天津医科大学学报,2024,30(02):122-127.[doi:10.20135/j.issn.1006-8147.2024.02.0122]
　LI Mei,LAI Jiadan,WEI Shiyao,et al.Research on recruitment of PD1+ CD8+ T lymphocytes mediated by IL4I1 derived from clear cell renal cell carcinoma[J].Journal of Tianjin Medical University,2024,30(02):122-127.[doi:10.20135/j.issn.1006-8147.2024.02.0122]
点击复制

肾透明细胞癌来源的IL4I1介导PD1+CD8+ T淋巴细胞募集的相关研究(PDF)
分享到：

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
30卷
期数:
2024年02期
页码:
122-127
栏目:
肿瘤疾病专题
出版日期:
2024-03-20

文章信息/Info

Title:
Research on recruitment of PD1+ CD8+ T lymphocytes mediated by IL4I1 derived from clear cell renal cell carcinoma
文章编号:
1006-8147（2024）02-0122-06
作者:
李美; 来佳丹; 魏诗瑶; 孟晋欢; 李常颖
（天津市泌尿外科研究所精准医学研究中心，天津医科大学第二医院泌尿外科，天津 300211）
Author(s):
LI Mei; LAI Jiadan; WEI Shiyao; MENG Jinhuan; LI Changying
（Precision Medicine Research Center，Tianjin Institute of Urology，Department of Urology，The Second Hospital of Tianjin Medical University，Tianjin 300211，China）
关键词:
肾透明细胞癌; IL4I1;  PD-1; CD8+T淋巴细胞; 趋化因子
Keywords:
clear cell renal cell carcinoma;  IL4I1;  PD1;  CD8+T lymphocytes;  chemokines
分类号:
R737.1
DOI:
10.20135/j.issn.1006-8147.2024.02.0122
文献标志码:
A
摘要:
目的：探讨肾透明细胞癌（ccRCC）来源的白细胞介素4诱导蛋白1（IL4I1）对表达PD1的 CD8+肿瘤浸润淋巴细胞（TILs）的诱导与募集作用。方法：利用公共数据库分析ccRCC组织中IL4I1的表达与CD8+ T淋巴细胞浸润及免疫功能相关分子表达的关系，通过免疫组织化学法进行验证；构建过表达IL4I1蛋白的769P细胞系并验证；荧光定量PCR （qPCR）和酶联免疫吸附试验（ELISA）检测过表达IL4I1 ccRCC细胞表达趋化因子的变化。结果：高表达IL4I1的ccRCC组织中有更多的CD8+ T淋巴细胞浸润（P=6.843×10-7），其浸润水平与IL4I1的表达水平呈正相关（r2=0.5764，P<0.001）；且浸润的CD8+T细胞多表达抑制型分子PD1。过表达IL4I1的ccRCC 769P细胞所表达的趋化因子配体（CCL2、CCL4、CCL5、CCL17）在mRNA水平显著下调（t=95.16、116.1、21.28、68.47，均P<0.05）。同时，细胞培养上清中CCL4、CCL5浓度明显升高（t=6.760、6.846，均P<0.05）。结论：ccRCC组织中IL4I1与PD1+CD8+T 淋巴细胞浸润密切相关，可能通过调控趋化因子的表达，参与免疫抑制型CD8+T淋巴细胞在肿瘤局部的募集。
Abstract:
Objective：To explore the role of interleukin-4-induced-1（IL4I1） in inducement and recruitment of CD8+ tumor-infiltrating lymphocytes（TILs） expressing PD1 in clear cell renal cell carcinoma（ccRCC）. Methods：The relationship between IL4I1 expression and CD8+ T lymphocyte infiltration and immune function related molecules expression in ccRCC tissues was analyzed using a public database，and verified by immunohistochemistry（IHC）. The 769P cell line overexpressing IL4I1 protein was constructed and verified. Quantitative real-time PCR（qPCR） and enzyme-linked immunosorbent assay（ELISA） were used to compare the expression of chemo-kines in ccRCC after IL4I1 overexpression. Results：CD8+T lymphocyte infiltration was more frequent in ccRCC tissues with high IL4I1 expression（P=6.843×10-7），and its infiltration level was positively correlated with IL4I1 expression level（P<0.001）. The infiltrating CD8+T cells mostly expressed the inhibitory molecule PD1. The mRNA levels of chemokine ligand（CCL2，CCL4，CCL5 and CCL17） were significantly down-regulated in ccRCC 769P cells after over-expression of IL4I1（t=95.16，116.1，21.28，68.47，all P<0.05）. At the same time，the concentrations of CCL4 and CCL5 in cell culture supernatant were significantly increased（t=6.760，6.846，both P<0.05）. Conclusion：IL4I1 is closely related to the infiltration of PD1+CD8+T lymphocytes in ccRCC tissues，and may participate in the recruitment of immunosuppressive CD8+T lymphocytes by regulating the expression of chemokines.

参考文献/References:

[1] GUO X，ZHANG Y，ZHENG L，et al. Global characterization of T cells in non-small-cell lung cancer by single-cell sequencing[J]. Nat Med，2018，24（7）：978-985.
[2] ZHANG L，YU X，ZHENG L，et al. Lineage tracking reveals dynamic relationships of T cells in colorectal cancer[J]. Nature，2018，564（7735）：268-272.
[3] YOST K E，SATPATHY A T，WELLS D K，et al. Clonal replacement of tumor-specific T cells following PD-1 blockade[J]. Nat Med，2019，25（8）：1251-1259.
[4] ZAJAC A J，BLATTMAN J N，MURALI-KRISHNA K，et al. Viral immune evasion due to persistence of activated T cells without effector function[J]. J Exp Med，1998，188（12）：2205-2213.
[5] WHERRY E J. T cell exhaustion[J]. Nat Immunol，2011，12（6）：492-499.
[6] SCHIETINGER A，GREENBERG P D. Tolerance and exhaustion：defining mechanisms of T cell dysfunction[J]. Trends Immunol，2014，35（2）：51-60.
[7] BARBER D L，WHERRY E J，MASOPUST D，et al. Restoring function in exhausted CD8 T cells during chronic viral infection[J]. Nature，2006，439（7077）：682-687.
[8] 魏诗瑶，来佳丹，李常颖. 白细胞介素4诱导蛋白1促进肾癌进展的实验研究[J]. 天津医科大学学报，2022，28（4）：366-371.
[9] 来佳丹，魏诗瑶，李常颖. 肾癌来源的IL4I1介导Treg诱导与募集的实验研究[J]. 天津医科大学学报，2023，29（3）：302-308.
[10] 杨谨，程婷婷，王丽娜，等. 肾透明细胞癌中AnnexinⅡ的表达及其临床意义[J]. 细胞与分子免疫学杂志，2012，28（1）：59-62.
[11] BOD L，LENGAGNE R，WROBEL L，et al. IL4-induced gene 1 promotes tumor growth by shaping the immune microenvironment in melanoma[J]. Oncoimmunology，2017，6（3）：e1278331.
[12] SADIK A，SOMARRIBAS PATTERSON L F，?魻ZT?譈RK S，et al. IL4I1 is a metabolic immune checkpoint that activates the AHR and promotes tumor progression[J]. Cell，2020，182（5）：1252-1270.e34.
[13] ZHAO H，TENG Y，HAO W，et al. Single-cell analysis revealed that IL4I1 promoted ovarian cancer progression[J]. J Transl Med，2021， 19（1）：454.
[14] KOMATSU M，YOSHIMARU T，MATSUO T，et al. Molecular features of triple negative breast cancer cells by genome-wide gene expression profiling analysis[J]. Int J Oncol，2013，42（2）：478-506.
[15] RAMSPOTT J P，BEKKAT F，BOD L，et al. Emerging role of IL-4-induced gene 1 as a pnostic biomarker affecting the local T-cell response in human cutaneous melanoma[J]. J Invest Dermatol，2018， 138（12）：2625-2634.
[16] FINAK G，BERTOS N，PEPIN F，et al. Stromal gene expression predicts clinical outcome in breast cancer[J]. Nat Med，2008，14（5）：518-527.
[17] SCARLATA C M，CELSE C，PIGNON P，et al. Differential expression of the immunosuppressive enzyme IL4I1 in human induced Aiolos+，but not natural Helios+，FOXP3+ Treg cells[J]. Eur J Immunol，2015，45（2）：474-479.
[18] LASOUDRIS F，COUSIN C，PREVOST-BLONDEL A，et al. IL4I1：an inhibitor of the CD8+ antitumor T-cell response in vivo[J]. Eur J Immunol，2011，41（6）：1629-1638.
[19] AUBATIN A，SAKO N，DECROUY X，et al. IL4-induced gene 1 is secreted at the immune synapse and modulates TCR activation independently of its enzymatic activity[J]. Eur J Immunol，2018，48（1）：106-119.
[20] SANTARLASCI V，MAGGI L，MAZZONI A，et al. IL-4-induced gene 1 maintains high Tob1 expression that contributes to TCR unresponsiveness in human T helper 17 cells[J]. Eur J Immunol，2014， 44（3）：654-661.

相似文献/References:

[1]张春锋,李长建,刘沛,等.KIF22在肾透明细胞癌中的表达及临床相关性研究[J].天津医科大学学报,2023,29(03):309.
　ZHANG Chun-feng,LI Chang-Jian,LIU Pei,et al.Expression and clinical correlation of KIF22 in clear cell renal cell carcinoma[J].Journal of Tianjin Medical University,2023,29(02):309.
[2]刘芬,李世宾,李晓石.人着丝粒蛋白E在人肾透明细胞癌中的表达及对细胞增殖的影响[J].天津医科大学学报,2023,29(06):594.
　LIU Fen,LI Shi-bin,LI Xiao-shi.Expression of human centromere protein E in human renal clear cell carcinoma and its effects on the cell proliferation[J].Journal of Tianjin Medical University,2023,29(02):594.
[3]魏诗瑶,来佳丹,李常颖.白细胞介素4诱导蛋白1促进肾癌进展的实验研究[J].天津医科大学学报,2022,28(04):366.
　WEI Shi-yao,LAI Jia-dan,LI Chang-ying.Research of interleukin-4-induced-1 promoting the progression of kidney clear cell carcinoma[J].Journal of Tianjin Medical University,2022,28(02):366.
[4]来佳丹,魏诗瑶,李常颖.肾癌来源的IL4I1介导Treg诱导与募集的实验研究[J].天津医科大学学报,2023,29(03):302.
　LAI Jia-dan,WEI Shi-yao,LI Chang-ying.Research on inducement and recruitment of Treg mediated by IL4I1 derived from renal cell carcinoma[J].Journal of Tianjin Medical University,2023,29(02):302.

备注/Memo

备注/Memo:
基金项目 天津医科大学第二医院重点实验室基金（ZDSYS202308，2017ZDSYS12）
作者简介 李美（1977-），女，护师，学士，研究方向：泌尿系统肿瘤微环境；通信作者：李常颖，E-mail：cli_cvrl@tmu.edu.cn。
更新日期/Last Update: 2024-03-20