Expression of PD-L1 and other immunotherapeutic targets in thymic epithelial tumors.
Expression of PD-L1 and other immunotherapeutic targets in thymic epithelial tumors.
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DOI：
10.1371/journal.pone.0182665
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Hellmann MD
中科院分区：
文献类型：
--
作者：
Arbour KC;Naidoo J;Steele KE;Ni A;Moreira AL;Rekhtman N;Robbins PB;Karakunnel J;Rimner A;Huang J;Riely GJ;Hellmann MD
胸腺是适应性免疫系统发育的关键器官，胸腺上皮肿瘤（胸腺瘤和胸腺癌）通常与自身免疫副肿瘤性疾病相关。然而，Teptide的免疫生物学没有得到很好的描述。对肿瘤微环境的评估，特别是对免疫靶点表达的评估，可以促进和优先考虑TcB患者的免疫治疗策略的发展。对23例WHO B2/B3型胸腺瘤（n = 12）和胸腺癌（n = 11）患者的肿瘤组织进行了鉴定，并对临床结局进行了注释。使用免疫组织化学半定量评估肿瘤细胞、CD 3+和CD 8+肿瘤浸润淋巴细胞（TIL）、共刺激（CD 137、GITR、ICOS）和共抑制免疫检查点分子（PD-1、CTLA-4、TIM-3）上膜PD-L1的表达。PD-L1阳性（≥ 25%的肿瘤膜表达）在胸腺瘤中常见（15/23，65%），与胸腺癌相比，在胸腺瘤中更常见（p<0.01），并且与较长的总生存期相关（p = 0.02）。TIM-3和GITR在所有的TCLs中表达，包括18/23和12/23分别具有至少中等/高表达。中/高CD 137表达与CD 8+相关（p = 0.01），中/高GITR表达与PD-1相关（p = 0.043）。甲状腺炎的特征是频繁的PD-L1表达，PD-L1与改善的生存相关，表明PD-L1信号传导可能在甲状腺炎中具有生物学重要性。免疫激活标志物和免疫靶分子在TcB中的稳健表达强调了开发抗PD-1/PD-L1疗法的潜力。
The thymus is a critical organ for the development of the adaptive immune system and thymic epithelial tumors (TETs; thymomas and thymic carcinomas) are often associated with auto-immune paraneoplastic conditions. However, the immunobiology of TETs is not well described. An evaluation of the tumor microenvironment, with particular focus on expression of immunotherapeutic targets, may facilitate and prioritize development of immunotherapy strategies for patients with TETs. Tumor tissues from 23 patients with WHO Type B2/B3 thymoma (n = 12) and thymic carcinoma (n = 11) were identified and clinical outcomes were annotated. The expression of membranous PD-L1 on tumor cells, CD3+ and CD8+ tumor infiltrating lymphocytes (TILs), co-stimulatory (CD137, GITR, ICOS), and co-inhibitory immune checkpoint molecules (PD-1, CTLA-4, TIM-3) were assessed semi-quantitatively using immunohistochemistry. PD-L1 positivity (≥ 25% of tumor membrane expression) was frequent in TETs (15/23, 65%), more common in thymomas compared to thymic carcinomas (p<0.01), and was associated with longer overall survival (p = 0.02). TIM-3 and GITR were expressed in all TETs, including 18/23 and 12/23 with at least moderate/high expression, respectively. Moderate/high CD137 expression correlated with CD8+ (p = 0.01) and moderate/high GITR expression co-associated with PD-1 (p = 0.043). TETs are characterized by frequent PD-L1 expression and PD-L1 is associated with improved survival, suggesting PD-L1 signaling may be biologically important in TETs. Robust expression of markers of immune activation and immunotherapeutic target molecules in TETs emphasizes the potential for development of anti-PD-1/PD-L1 therapies.
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DOI：
10.1056/nejmoa1504030
发表时间：
2015-07-02
期刊：
The New England journal of medicine
影响因子：
--
作者：
Larkin J;Chiarion-Sileni V;Gonzalez R;Grob JJ;Cowey CL;Lao CD;Schadendorf D;Dummer R;Smylie M;Rutkowski P;Ferrucci PF;Hill A;Wagstaff J;Carlino MS;Haanen JB;Maio M;Marquez-Rodas I;McArthur GA;Ascierto PA;Long GV;Callahan MK;Postow MA;Grossmann K;Sznol M;Dreno B;Bastholt L;Yang A;Rollin LM;Horak C;Hodi FS;Wolchok JD
通讯作者：
Wolchok JD
DOI：
10.1097/jto.0000000000000363
发表时间：
2014-12
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Litvak AM;Woo K;Hayes S;Huang J;Rimner A;Sima CS;Moreira AL;Tsukazan M;Riely GJ
通讯作者：
Riely GJ
DOI：
10.1056/nejmoa1510665
发表时间：
2015-11-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Motzer RJ;Escudier B;McDermott DF;George S;Hammers HJ;Srinivas S;Tykodi SS;Sosman JA;Procopio G;Plimack ER;Castellano D;Choueiri TK;Gurney H;Donskov F;Bono P;Wagstaff J;Gauler TC;Ueda T;Tomita Y;Schutz FA;Kollmannsberger C;Larkin J;Ravaud A;Simon JS;Xu LA;Waxman IM;Sharma P;CheckMate 025 Investigators
通讯作者：
CheckMate 025 Investigators
影响因子：
11.5
作者：
Yokoyama, Shintaro;Miyoshi, Hiroaki;Ohshima, Koichi
通讯作者：
Ohshima, Koichi
影响因子：
45.3
作者：
Loehrer, PJ;Chen, M;Johnson, D
通讯作者：
Johnson, D