Immune response drives outcomes in prostate cancer: implications for immunotherapy.
Immune response drives outcomes in prostate cancer: implications for immunotherapy.
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DOI：
10.1002/1878-0261.12887
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发表时间：
2021-05
影响因子：
6.6
通讯作者：
Liang C
中科院分区：
文献类型：
--
作者：
Meng J;Zhou Y;Lu X;Bian Z;Chen Y;Zhou J;Zhang L;Hao Z;Zhang M;Liang C
免疫微环境的异质性导致免疫检查点阻断治疗的不同反应。我们旨在建立一个强大的分子分类系统，以研究前列腺癌患者免疫微环境亚型与预后的相关性，以及对免疫检查点阻断治疗的治疗反应。共有1557名前列腺癌患者入组，包括来自我们研究所的69名真实样本（标题为AHMU - PC队列）。采用非负矩阵分解算法对患者进行虚拟显微解剖。免疫富集的特征是T细胞、B细胞、NK细胞和巨噬细胞相关特征的高富集，由此将患者分为非免疫和免疫两类。随后，基于基质特征（以WNT/TGF - β、TGF - β1和C - ECM特征激活为代表），将免疫类分为免疫激活亚型和免疫抑制亚型。大约14.9%至24.3%的患者属于免疫激活亚型，这与良好的无复发生存结果相关。此外，免疫激活亚型的患者预计从抗PD‐1/PD‐L1治疗中获益更多。总之，我们的研究确定了一种与临床预后密切相关的新型免疫分子分类器，并为前列腺癌患者的免疫治疗策略提供了新的见解。本研究在分析1557例前列腺癌病例的基础上确定了一种新的免疫分子分类器。免疫激活亚组患者预后良好，抗PD‐1/PD‐L1治疗效果更好。我们的研究结果表明，免疫反应驱动前列腺癌的临床结果，突出了前列腺癌患者免疫治疗的重要意义。
The heterogeneity of the immune microenvironment leads to different responses in immune checkpoint blockade therapy. We aimed to propose a robust molecular classification system to investigate the relevance of the immune microenvironment subtype and prognosis of prostate cancer patients, as well as the therapeutic response to immune checkpoint blockade therapy. A total of 1,557 prostate cancer patients were enrolled, including 69 real‐world samples from our institute (titled the AHMU‐PC cohort). The non‐negative matrix factorization algorithm was employed to virtually microdissect patients. The immune enrichment was characterized by a high enrichment of T cell‐, B cell‐, NK cell‐, and macrophage‐associated signatures, by which patients were subclassified into nonimmune and immune classes. Subsequently, the immune class was dichotomized into immune‐activated and immune‐suppressed subtypes based on the stromal signature, represented by the activation of WNT/TGF‐β, TGF‐β1, and C‐ECM signatures. Approximately 14.9% to 24.3% of patients belonged to the immune‐activated subtype, which was associated with favorable recurrence‐free survival outcomes. In addition, patients in the immune‐activated subtype were predicted to benefit more from anti‐PD‐1/PD‐L1 therapy. In conclusion, our study identifies a novel immune molecular classifier that is closely related to clinical prognosis and provides novel insights into immunotherapeutic strategies for prostate cancer patients. This study identifies a novel immune molecular classifier for prostate cancer based on the analysis of 1,557 cases. Patients in the immune activated subgroup were associated with favorable prognosis and better outcomes of anti‐PD‐1/PD‐L1 therapy. Our findings suggest that the immune response drives clinical outcomes in prostate cancer, highlighting important implications for immunotherapy in patients with prostate cancer.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
64.5
作者：
Malta TM;Sokolov A;Gentles AJ;Burzykowski T;Poisson L;Weinstein JN;Kamińska B;Huelsken J;Omberg L;Gevaert O;Colaprico A;Czerwińska P;Mazurek S;Mishra L;Heyn H;Krasnitz A;Godwin AK;Lazar AJ;Cancer Genome Atlas Research Network;Stuart JM;Hoadley KA;Laird PW;Noushmehr H;Wiznerowicz M
通讯作者：
Wiznerowicz M
DOI：
10.1038/ncpuro1296
发表时间：
2009-02
期刊：
NATURE CLINICAL PRACTICE UROLOGY
影响因子：
--
作者：
Harris, William P.;Mostaghel, Elahe A.;Nelson, Peter S.;Montgomery, Bruce
通讯作者：
Montgomery, Bruce
影响因子：
7.2
作者：
Knudson KM;Hicks KC;Luo X;Chen JQ;Schlom J;Gameiro SR
通讯作者：
Gameiro SR
DOI：
10.1073/pnas.0308531101
发表时间：
2004-03-23
影响因子：
11.1
作者：
Brunet, JP;Tamayo, P;Mesirov, JP
通讯作者：
Mesirov, JP