Combination Biomarker of Immune Checkpoints Predict Prognosis of Urothelial Carcinoma

被引:2
作者
Tsai, Chung-Ying [1 ]
Chi, Hsiang-Cheng [2 ,3 ]
Wu, Ren-Chin [4 ,5 ]
Weng, Cheng-Hao [1 ]
Tai, Tzong-Shyuan [6 ]
Lin, Chan-Yu [1 ]
Chen, Tai-Di [4 ]
Wang, Ya-Hui [7 ]
Chou, Li-Fang [1 ]
Hsu, Shen-Hsing [1 ]
Lin, Po-Hung [8 ,9 ,10 ]
Pang, See-Tong [8 ,10 ]
Yang, Hung-Yu [1 ,6 ,11 ]
机构
[1] Chang Gung Univ, Kidney Res Ctr, Dept Nephrol, Chang Gung Mem Hosp,Coll Med, Taoyuan 333, Taiwan
[2] China Med Univ, Grad Inst Integrated Med, Taichung 404, Taiwan
[3] China Med Univ, Chinese Med Res Ctr, Taichung 404, Taiwan
[4] Chang Gung Mem Hosp, Dept Pathol, Taoyuan 333, Taiwan
[5] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA
[6] Chang Gung Mem Hosp, Adv Immunol Lab, Taoyuan 333, Taiwan
[7] Chang Gung Univ, Chang Gung Mem Hosp, Inst Stem Cell & Translat Canc Res, Taoyuan 333, Taiwan
[8] Chang Gung Univ, Grad Inst Clin Med Sci, Coll Med, Taoyuan 333, Taiwan
[9] Chang Gung Univ, Coll Med, Sch Med, Taoyuan 333, Taiwan
[10] Chang Gung Mem Hosp, Dept Surg, Div Urol, Taoyuan 333, Taiwan
[11] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD 21205 USA
关键词
urothelial carcinoma; regulatory T cells; immune checkpoints; CD276; TIM-3; REGULATORY T-CELLS; BLADDER-CANCER; EXPRESSION; TOLERANCE; B7-H3; ASSOCIATION; PATHWAYS; TREG;
D O I
10.3390/biomedicines10010008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In contrast to Western counties, the incidence of urothelial carcinoma (UC) remains mar-edly elevated in Taiwan. Regulatory T cells (Tregs) play a crucial role in limiting immune responses within the tumor microenvironment. To elucidate the relationship between immune checkpoints in the tumor immune microenvironment and UC progression, we utilize the Gene Expression Omnibus (GEO) to analyze a microarray obtained from 308 patients with UC. We observed that the expression level of CD276 or TIM-3 was positively correlated with late-stage UC and poor prognosis. Patients with simultaneously high CD276 and TIM-3 expression in tumors have significantly reduced both univariate and multivariate survival, indicating that mRNA levels of these immune checkpoints could be independent prognostic biomarkers for UC overall survival and recurrence. Our cohort study showed rare CD8+ cytotoxic T-cells and Tregs infiltration during early-stage UC-known as cold tumors. Approximately 30% of late-stage tumors exhibited highly infiltrated cytotoxic T cells with high PD-1 and FOXP3 expression, which implied that cytotoxic T cells were inhibited in the advanced UC microenvironment. Collectively, our findings provide a better prognosis prediction by combined immune checkpoint biomarkers and a basis for early-stage UC standard treatment to convert cold tumors into hot tumors, followed by immune checkpoint therapy.
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页数:10
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