Immune response drives outcomes in prostate cancer: implications for immunotherapy.

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Tytuł:: Immune response drives outcomes in prostate cancer: implications for immunotherapy.
Autorzy:: Meng J; Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; Institute of Urology & Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China.
Zhou Y; Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, China.
Lu X; State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, China.
Bian Z; Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; Institute of Urology & Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China.
Chen Y; Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; Institute of Urology & Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China.
Zhou J; Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; Institute of Urology & Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China.
Zhang L; Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; Institute of Urology & Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China.
Hao Z; Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; Institute of Urology & Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China.
Zhang M; Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; Institute of Urology & Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China.; Urology Institute of Shenzhen University, The Third Affiliated Hospital of Shenzhen University, Shenzhen University, China.
Liang C; Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.; Institute of Urology & Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China.
Źródło:: Molecular oncology [Mol Oncol] 2021 May; Vol. 15 (5), pp. 1358-1375. Date of Electronic Publication: 2020 Dec 29.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: 2017- : Hoboken, New Jersey : John Wiley & Sons, Inc.
Original Publication: Amsterdam : Elsevier
MeSH Terms:: Immunity/*physiology
Prostatic Neoplasms/*diagnosis
Prostatic Neoplasms/*immunology
Adenocarcinoma/diagnosis ; Adenocarcinoma/genetics ; Adenocarcinoma/immunology ; Adenocarcinoma/therapy ; Aged ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/immunology ; Cohort Studies ; Gene Expression Regulation, Neoplastic ; Humans ; Immunotherapy ; Killer Cells, Natural/metabolism ; Killer Cells, Natural/pathology ; Lymphocytes, Tumor-Infiltrating/immunology ; Lymphocytes, Tumor-Infiltrating/metabolism ; Male ; Middle Aged ; Prognosis ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/therapy ; Treatment Outcome ; Tumor Microenvironment/genetics ; Tumor Microenvironment/immunology
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Contributed Indexing:: Keywords: immune checkpoint blockade therapy; immune molecular subclassification system; immunotherapy; non-negative matrix factorization; prostate cancer
Substance Nomenclature:: 0 (Biomarkers, Tumor)
Entry Date(s):: Date Created: 20201218 Date Completed: 20220331 Latest Revision: 20240402
Update Code:: 20240402
PubMed Central ID:: PMC8096785
DOI:: 10.1002/1878-0261.12887
PMID:: 33338321
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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.
(© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.)

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