期刊
MOLECULAR ONCOLOGY
卷 15, 期 5, 页码 1358-1375出版社
WILEY
DOI: 10.1002/1878-0261.12887
关键词
immune checkpoint blockade therapy; immune molecular subclassification system; immunotherapy; non‐ negative matrix factorization; prostate cancer
类别
资金
- National Natural Science Foundation of China [81802827, 81630019]
- Scientific Research Foundation of the Institute for Translational Medicine of Anhui Province [2017ZHYX02]
- Natural Science Foundation of Guangdong Province, China [2017A030313800]
- Key Project of Provincial Natural Science Research Project of Anhui Colleges [KJ2019A0278]
- Supporting Project for Distinguished Young Scholar of Anhui Colleges [gxyqZD2019018]
- 2017 Anhui Province special program for guiding local science and technology development by the central government [2017070802D148]
A new immune molecular classifier was proposed in this study to classify prostate cancer patients into different immune-activated and immune-suppressed subtypes. The immune-activated subtype was found to be associated with favorable recurrence-free survival outcomes and was predicted to benefit more from anti-PD-1/PD-L1 therapy.
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-beta, TGF-beta 1, 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.
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