PD-L1 Expression Is Associated with FOXP3+ Regulatory T-Cell Infiltration of Soft Tissue Sarcoma and Poor Patient Prognosis.
PD-L1 Expression Is Associated with FOXP3+ Regulatory T-Cell Infiltration of Soft Tissue Sarcoma and Poor Patient Prognosis.
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PD-L1 表达与软组织肉瘤的 FOXP3 调节性 T 细胞浸润和患者预后不良相关
DOI：
10.7150/jca.18683
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发表时间：
2017
影响因子：
3.9
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Que Y;Xiao W;Guan YX;Liang Y;Yan SM;Chen HY;Li QQ;Xu BS;Zhou ZW;Zhang X
背景：程序性死亡配体1（PD-L1）通过不同途径参与抗肿瘤免疫，是免疫应答的负性介质。最近的研究报道，PD-L1在调节性T细胞（Tcells）的功能中起着关键作用。尽管在几种癌症中发现FOXP 3 + Tregs浸润和PD-L1表达增加，但它们与软组织肉瘤的相关性仍然未知。研究方法：我们纳入了2000-2010年在中国广州中山大学肿瘤防治中心诊断并接受广泛根治性切除术的163例软组织肉瘤患者。PD-L1和FOXP 3表达通过免疫组织化学进行评价。研究其表达与临床病理特征的相关性。结果：163例STS中PD-L1阳性19例（11.7%），FOXP 3 + Treg高表达41例（25.2%）。鉴定了STS中PD-L1表达与FOXP 3 +Treg浸润之间的显著相关性（r=0.450，p<0.001）。在单因素分析中，PD-L1表达与高肿瘤分级和患者年龄显著相关，而肿瘤浸润性T细胞中FOXP 3+的存在与患者年龄、高肿瘤分期、高肿瘤分级和肿瘤深度显著相关。多因素分析显示PD-L1和FOXP 3作为独立的预后指标与OS和DFS显著相关。结论：PD-L1和FOXP 3 + TGFAP可能协同促进软组织肉瘤的免疫逃逸。阻断PD-L1/PD-1与同时耗尽TdR的组合策略可能显示出增强这些患者的治疗功效的前景。
Background: Programmed death ligand-1(PD-L1) functions as a negative mediator of immune response through different pathways in anti-tumor immunity. Recent studies have reported that PD-L1 plays a pivotal role in the function of regulatory T-cells (Tregs). Although increases in FOXP3+ Tregs infiltration and PD-L1 expression have been revealed in several cancers, their correlation with soft tissue sarcoma remains unknown. Methods: We included 163 cases of soft tissue sarcoma who were diagnosed and underwent extensive and radical resection at the Sun Yat-sen University Cancer Center, Guangzhou, China, from 2000-2010. PD-L1 and FOXP3 expression was evaluated by immunohistochemistry. Correlation between their expressions and associations with clinicopathological features were studied. Results: Among 163 STS samples, 19 (11.7%) exhibited PD-L1 positivity, and 41 (25.2%) cases expressed high FOXP3+ Treg infiltration. Significant correlation between PD-L1 expression and FOXP3+Treg infiltration in STS was identified (r=0.450, p<0.001). In univariate analysis, PD-L1 expression was significantly associated with high tumor grade and the age of patients, while the presence of FOXP3+ in tumor infiltrating Tregs was significantly associated with the age of patients, high tumor stage, higher tumor grade and tumor depth. Multivariate analysis revealed PD-L1 and FOXP3 as independent prognostic indicators significantly associated with OS and DFS. Conclusions: Our study revealed that PD-L1 and FOXP3+Tregs may work synergistically in promoting immune evasion of the tumors in soft tissue sarcoma. A combined strategy to block PD-L1/PD-1 with simultaneous depletion of Tregs may show promise in enhancing the therapeutic efficacy of these patients.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
影响因子：
--
作者：
Maki RG;Jungbluth AA;Gnjatic S;Schwartz GK;D'Adamo DR;Keohan ML;Wagner MJ;Scheu K;Chiu R;Ritter E;Kachel J;Lowy I;Old LJ;Ritter G
通讯作者：
Ritter G
影响因子：
8.4
作者：
Droeser, Raoul A.;Hirt, Christian;Tornillo, Luigi
通讯作者：
Tornillo, Luigi
影响因子：
--
作者：
Chen, Yan-bin;Mu, Chuan-Yong;Huang, Jian-An
通讯作者：
Huang, Jian-An
DOI：
10.1084/jem.20090847
发表时间：
2009-12-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Francisco LM;Salinas VH;Brown KE;Vanguri VK;Freeman GJ;Kuchroo VK;Sharpe AH
通讯作者：
Sharpe AH