PMID- 38470096
OWN - NLM
STAT- MEDLINE
DCOM- 20240313
LR  - 20240418
IS  - 1755-5949 (Electronic)
IS  - 1755-5930 (Print)
IS  - 1755-5930 (Linking)
VI  - 30
IP  - 3
DP  - 2024 Mar
TI  - Exosome-transmitted podoplanin promotes tumor-associated macrophage-mediated 
      immune tolerance in glioblastoma.
PG  - e14643
LID - 10.1111/cns.14643 [doi]
LID - e14643
AB  - AIMS: Glioblastoma is the most frequent and aggressive primary brain tumor, 
      characterized by rapid disease course and poor treatment responsiveness. The 
      abundance of immunosuppressive macrophages in glioblastoma challenges the 
      efficacy of novel immunotherapy. METHODS: Bulk RNA-seq and single-cell RNA-seq of 
      glioma patients from public databases were comprehensively analyzed to illustrate 
      macrophage infiltration patterns and molecular characteristics of podoplanin 
      (PDPN). Multiplexed fluorescence immunohistochemistry staining of PDPN, GFAP, 
      CD68, and CD163 were performed in glioma tissue microarray. The impact of PDPN on 
      macrophage immunosuppressive polarization was investigated using a co-culture 
      system. Bone marrow-derived macrophages (BMDMs) and OT-II T cells isolated from 
      BALB/c and OT-II mice respectively were co-cultured to determine T-cell 
      adherence. Pathway alterations were probed through RNA sequencing and western 
      blot analyses. RESULTS: Our findings demonstrated that PDPN is notably correlated 
      with the expression of CD68 and CD163 in glioma tissues. Additionally, 
      macrophages phagocytosing PDPN-containing EVs (EVs(PDPN) ) from GBM cells 
      presented increased CD163 expression and augmented secretion of 
      immunoregulatory cytokine (IL-6, IL-10, TNF-alpha, and TGF-beta1). PDPN within EVs was 
      also associated with enhanced phagocytic activity and reduced MHC II expression 
      in macrophages, compromising CD4(+) T-cell activation. CONCLUSIONS: This 
      investigation underscores that EVs(PDPN) derived from glioblastoma cells 
      contributes to M2 macrophage-mediated immunosuppression and is a potential 
      prognostic marker and therapeutic target in glioblastoma.
CI  - (c) 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & 
      Sons Ltd.
FAU - Wu, Mengwan
AU  - Wu M
AD  - Department of Oncology, Sichuan Academy of Medical Sciences, Sichuan Provincial 
      People's Hospital, School of Medicine, University of Electronic Science and 
      Technology of China, Chengdu, Sichuan, China.
AD  - Yu-Yue Pathology Scientific Research Center, Chongqing, China.
AD  - Jinfeng Laboratory, Chongqing, China.
FAU - Shi, Ying
AU  - Shi Y
AD  - Department of Oncology, Sichuan Academy of Medical Sciences, Sichuan Provincial 
      People's Hospital, School of Medicine, University of Electronic Science and 
      Technology of China, Chengdu, Sichuan, China.
FAU - Liu, Yuyang
AU  - Liu Y
AD  - Department of Neurosurgery, 920th Hospital of Joint Logistics Support Force, 
      Kunming, China.
FAU - Huang, Hongxiang
AU  - Huang H
AD  - Department of Oncology, The First Affiliated Hospital, Nanchang University, 
      Nanchang, China.
FAU - Che, Jiajia
AU  - Che J
AD  - Department of Oncology, Sichuan Academy of Medical Sciences, Sichuan Provincial 
      People's Hospital, School of Medicine, University of Electronic Science and 
      Technology of China, Chengdu, Sichuan, China.
FAU - Shi, Jing
AU  - Shi J
AD  - Department of Neurosurgery, 920th Hospital of Joint Logistics Support Force, 
      Kunming, China.
FAU - Xu, Chuan
AU  - Xu C
AUID- ORCID: 0000-0002-5320-2277
AD  - Department of Oncology, Sichuan Academy of Medical Sciences, Sichuan Provincial 
      People's Hospital, School of Medicine, University of Electronic Science and 
      Technology of China, Chengdu, Sichuan, China.
AD  - Yu-Yue Pathology Scientific Research Center, Chongqing, China.
AD  - Jinfeng Laboratory, Chongqing, China.
LA  - eng
GR  - 2023YFC3402100/National Key Research and Development Program of China/
GR  - 82203539/The National Natural Science Foundation of China/
GR  - 92259102/The National Natural Science Foundation of China/
GR  - ZYGX2021YGCX004/Medico-Engineering Cooperation Funds from University of 
      Electronic Science and Technology of China/
GR  - ZYGX2021YGCX018/Medico-Engineering Cooperation Funds from University of 
      Electronic Science and Technology of China/
GR  - 2022X045/Funds from Sichuan Academy of Medical Sciences, Sichuan Provincial 
      People's Hospital/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - CNS Neurosci Ther
JT  - CNS neuroscience & therapeutics
JID - 101473265
RN  - 0 (Transcription Factors)
RN  - 0 (PDPN protein, human)
RN  - 0 (Gp38 protein, mouse)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - *Exosomes/metabolism
MH  - *Glioblastoma/pathology
MH  - *Glioma/metabolism
MH  - Immune Tolerance
MH  - Transcription Factors
MH  - Tumor-Associated Macrophages/metabolism/pathology
PMC - PMC10929222
OTO - NOTNLM
OT  - GBM
OT  - PDPN
OT  - exosome
OT  - glioma
OT  - immunosuppressive TME
OT  - macrophage
COIS- The authors declare no conflicts of interest.
EDAT- 2024/03/12 12:44
MHDA- 2024/03/13 06:46
PMCR- 2024/03/12
CRDT- 2024/03/12 08:43
PHST- 2024/01/11 00:00 [revised]
PHST- 2023/11/17 00:00 [received]
PHST- 2024/01/29 00:00 [accepted]
PHST- 2024/03/13 06:46 [medline]
PHST- 2024/03/12 12:44 [pubmed]
PHST- 2024/03/12 08:43 [entrez]
PHST- 2024/03/12 00:00 [pmc-release]
AID - CNS14643 [pii]
AID - 10.1111/cns.14643 [doi]
PST - ppublish
SO  - CNS Neurosci Ther. 2024 Mar;30(3):e14643. doi: 10.1111/cns.14643.