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A Crosstalk Between Castration-Resistant Prostate Cancer Cells, M2 Macrophages, and NK Cells: Role of the ATM-PI3K/AKT-PD-L1 Pathway.
Jin, Hongliang; Zhu, Jin; Xuan, Rui; Zhou, Yibin; Xue, Boxin; Yang, Dongrong; Gao, Jie; Zang, Yachen; Xu, Lijun.
Afiliação
  • Jin H; Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
  • Zhu J; Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
  • Xuan R; Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
  • Zhou Y; Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
  • Xue B; Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
  • Yang D; Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
  • Gao J; Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
  • Zang Y; Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
  • Xu L; Department of Urology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Immunol Invest ; 52(8): 941-965, 2023 Nov.
Article em En | MEDLINE | ID: mdl-37732622
ABSTRACT
Castration-resistant prostate cancer (CRPC) in males is associated with a poor prognosis and a higher risk of treatment-related adverse effects, with high mortality among cancers globally. It is thus imperative to explore novel potential molecules with dual therapeutic and biomarker functions. Based on the recent research findings, the expression levels of ataxia telangiectasia mutant kinase (ATM) in prostate cancer (PC) tissues collected from CRPC patients were higher than hormone-dependent PC patients. Using CRPC cell lines (C4-2 and CWR22Rv1), the transwell chamber experiments revealed ATM promoted macrophage recruitment in CRPC cells in vitro via C-X-C motif chemokine ligand 12 (CXCL12). Further in vitro investigations demonstrated that polarized macrophages prevented NK cell recruitment and reduced the immunocidal activity of NK cells against CRPC cell lines. Moreover, ATM boosted programmed death receptor ligand 1 (PD-L1) expression while inhibiting NK group 2D (NKG2D) ligand expression in selected cell lines via PI3K/AKT signaling pathway. The in vivo investigations revealed ATM induced proliferation of CRPC and macrophage recruitment, while the NK cell recruitment was found to suppress ATM expression and CRPC proliferation. In conclusion, it could be demonstrated that inhibiting ATM increased the susceptibility of CRPC to NK cell inhibitors by dampening the CXCL12 and PI3K/AKT-PD-L1 pathways, thereby offering a novel and individualized treatment protocol for treating CRPC.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias de Próstata Resistentes à Castração Tipo de estudo: Guideline / Prognostic_studies Limite: Humans / Male Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias de Próstata Resistentes à Castração Tipo de estudo: Guideline / Prognostic_studies Limite: Humans / Male Idioma: En Ano de publicação: 2023 Tipo de documento: Article