B7 score and T cell infiltration stratify immune status in prostate cancer.
B7 score and T cell infiltration stratify immune status in prostate cancer.
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B7 评分和 T 细胞浸润对前列腺癌的免疫状态进行分层
DOI：
10.1136/jitc-2021-002455
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发表时间：
2021-08
影响因子：
10.9
通讯作者：
Huang H
中科院分区：
文献类型：
--
作者：
Zhou Q;Li K;Lai Y;Yao K;Wang Q;Zhan X;Peng S;Cai W;Yao W;Zang X;Xu K;Huang J;Huang H
尽管免疫检查点抑制剂（ICI），特别是程序性细胞死亡蛋白1（PD-1）/程序性死亡配体1（PD-L1）轴阻断剂，对许多恶性肿瘤表现出突出的抗肿瘤作用，但其对前列腺癌（PCa）患者的获益有些微不足道。本研究旨在评估B7-H3或HHLA 2作为PCa替代免疫靶点的可行性。采用免疫组化方法评价PD-L1、B7-H3和HHLA 2的表达模式以及CD 8+和Foxp 3+淋巴细胞在两个独立队列的239例PCa组织中的浸润情况。探讨了B7-H3和HLA 2与临床病理特征的相关性，包括CD 8+和Foxp 3+肿瘤浸润淋巴细胞（TIL）的存在。HHLA 2在PCa组织中的表达明显高于PD-L1，但低于B7-H3。B7-H3和HHLA 2的高表达与Gleason评分、肿瘤分期、淋巴结转移、总生存率（OS）和肿瘤特异性生存率（CSS）显著相关。此外，高B7评分（定义为高B7-H3表达和/或高HHLA 2表达）是PCa的独立预后预测因子。值得注意的是，高B7评分与CD 8 + TIL呈负相关。重要的是，基于B7评分和CD 8 + TIL的新免疫分类成功地对PCa中的OS和CSS进行了分层。B7-H3和HHLA 2对免疫抑制微环境有重要影响，B7评分可作为PCa的独立预后因素。B7评分结合CD 8 + TIL可作为一种新的免疫分类，用于PCa患者死亡风险分层，尤其是癌症相关死亡。这些发现可能会提供见解，可以改善未来对PCa免疫相关综合治疗的反应。
Although immune checkpoint inhibitors (ICIs), especially programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis blockers, exhibit prominent antitumor effects against numerous malignancies, their benefit for patients with prostate cancer (PCa) has been somewhat marginal. This study aimed to assess the feasibility of B7-H3 or HHLA2 as alternative immunotherapeutic targets in PCa. Immunohistochemistry was performed to evaluate the expression pattern of PD-L1, B7-H3 and HHLA2 and the infiltration of CD8+ and Foxp3+ lymphocytes in 239 PCa tissues from two independent cohorts. The correlations between B7-H3 and HHLA2 and clinicopathological features, including the presence of CD8+ and Foxp3+ tumor-infiltrating lymphocytes (TILs), were explored. HHLA2 expression was much higher than PD-L1 expression but lower than B7-H3 expression in PCa tissues. High expression of both B7-H3 and HHLA2 was significantly associated with higher Gleason score and tumor stage, lymph node metastasis and dismal overall survival (OS) and cancer-specific survival (CSS). Moreover, a high B7 score, defined as high B7-H3 expression and/or high HHLA2 expression, was an independent prognostic predictor for PCa. Of note, a high B7 score was negatively correlated with CD8+ TILs. Importantly, a new immune classification, based on the B7 score and CD8+ TILs, successfully stratified OS and CSS in PCa. Both B7-H3 and HHLA2 have a critical impact on the immunosuppressive microenvironment, and the B7 score could be used as an independent prognostic factor for PCa. The B7 score combined with CD8+ TILs could be used as a new immune classification to stratify the risk of death, especially cancer-related death, for patients with PCa. These findings may provide insights that could improve response to immune-related comprehensive therapy for PCa in the future.
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DOI：
10.1158/1078-0432.ccr-15-3071
发表时间：
2017-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Cheng H;Janakiram M;Borczuk A;Lin J;Qiu W;Liu H;Chinai JM;Halmos B;Perez-Soler R;Zang X
通讯作者：
Zang X
影响因子：
10.9
作者：
Läubli H;Balmelli C;Kaufmann L;Stanczak M;Syedbasha M;Vogt D;Hertig A;Müller B;Gautschi O;Stenner F;Zippelius A;Egli A;Rothschild SI
通讯作者：
Rothschild SI
DOI：
10.1073/pnas.0405259101
发表时间：
2004-08-31
影响因子：
11.1
作者：
Suh, WK;Wang, SX;Mak, TW
通讯作者：
Mak, TW
影响因子：
4.4
作者：
Prasad, DVR;Nguyen, T;Dong, C
通讯作者：
Dong, C
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