PMID- 37732622
OWN - NLM
STAT- MEDLINE
DCOM- 20231219
LR  - 20231219
IS  - 1532-4311 (Electronic)
IS  - 0882-0139 (Linking)
VI  - 52
IP  - 8
DP  - 2023 Nov
TI  - A Crosstalk Between Castration-Resistant Prostate Cancer Cells, M2 Macrophages, 
      and NK Cells: Role of the ATM-PI3K/AKT-PD-L1 Pathway.
PG  - 941-965
LID - 10.1080/08820139.2023.2258930 [doi]
AB  - 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.
FAU - Jin, Hongliang
AU  - Jin H
AD  - Department of Urology, The Second Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu, China.
FAU - Zhu, Jin
AU  - Zhu J
AD  - Department of Urology, The Second Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu, China.
FAU - Xuan, Rui
AU  - Xuan R
AD  - Department of Urology, The Second Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu, China.
FAU - Zhou, Yibin
AU  - Zhou Y
AD  - Department of Urology, The Second Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu, China.
FAU - Xue, Boxin
AU  - Xue B
AD  - Department of Urology, The Second Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu, China.
FAU - Yang, Dongrong
AU  - Yang D
AD  - Department of Urology, The Second Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu, China.
FAU - Gao, Jie
AU  - Gao J
AD  - Department of Urology, The Second Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu, China.
FAU - Zang, Yachen
AU  - Zang Y
AD  - Department of Urology, The Second Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu, China.
FAU - Xu, Lijun
AU  - Xu L
AD  - Department of Urology, The Second Affiliated Hospital of Soochow University, 
      Suzhou, Jiangsu, China.
LA  - eng
PT  - Journal Article
DEP - 20231124
PL  - England
TA  - Immunol Invest
JT  - Immunological investigations
JID - 8504629
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
RN  - EC 2.7.11.1 (ATM protein, human)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Ligands)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Humans
MH  - Male
MH  - Ataxia Telangiectasia Mutated Proteins/metabolism
MH  - B7-H1 Antigen/metabolism
MH  - Cell Line, Tumor
MH  - Killer Cells, Natural
MH  - Ligands
MH  - Macrophages/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *Prostatic Neoplasms, Castration-Resistant/drug therapy/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
OTO - NOTNLM
OT  - Ataxia telangiectasia mutated kinase (ATM)
OT  - PI3K/AKT pathway
OT  - castration-resistant prostate cancer (CRPC)
OT  - macrophage recruitment
OT  - natural killer cells
OT  - programmed death receptor ligand 1 (PD-L1)
EDAT- 2023/09/21 12:42
MHDA- 2023/11/27 12:43
CRDT- 2023/09/21 08:07
PHST- 2023/11/27 12:43 [medline]
PHST- 2023/09/21 12:42 [pubmed]
PHST- 2023/09/21 08:07 [entrez]
AID - 10.1080/08820139.2023.2258930 [doi]
PST - ppublish
SO  - Immunol Invest. 2023 Nov;52(8):941-965. doi: 10.1080/08820139.2023.2258930. Epub 
      2023 Nov 24.