PMID- 33613696
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220420
IS  - 1758-8340 (Print)
IS  - 1758-8359 (Electronic)
IS  - 1758-8340 (Linking)
VI  - 13
DP  - 2021
TI  - Methotrexate enhances antigen presentation and maturation of tumour 
      antigen-loaded dendritic cells through NLRP3 inflammasome activation: a strategy 
      for dendritic cell-based cancer vaccine.
PG  - 1758835920987056
LID - 10.1177/1758835920987056 [doi]
LID - 1758835920987056
AB  - BACKGROUND: Dendritic cells (DCs) are antigen-presenting cells that play a 
      pivotal role in adaptive cell-mediated immunity by priming and activating T cells 
      against specific tumour and pathogenic antigens. Methotrexate (MTX), a folate 
      derivative, functions as an immunoregulatory agent. However, the possible effect 
      of MTX on tumour antigen-loaded DCs has not yet been investigated. METHODS: We 
      analysed the effect of MTX on the maturation and function of DCs along with 
      tumour cell lysates (TCLs). Using bone marrow-derived DCs, we investigated the 
      effect of MTX combined TCL-loaded DCs on T cells priming and proliferation. We 
      also tested the anti-tumour immune effect on DCs when treated with MTX and/or TCL 
      in vivo. RESULTS: MTX combined with TCL not only enhanced DC maturation and 
      stimulated cytokine release but also promoted CD8(+) T cell activation and 
      proliferation. The latter was associated with increased tumour antigen uptake and 
      cross-presentation to T cells. Mechanistically, DC maturation and antigen 
      presentation were partly modulated by NLRP3 inflammasome activation. Furthermore, 
      immunisation of mice with MTX and TCL-pulsed DCs before a tumour challenge 
      significantly delayed tumour onset and retarded its growth. This protective 
      effect was due to priming of IFN-gamma releasing CD8(+) T cells and enhanced killing 
      of tumour cells by cytotoxic T lymphocytes isolated from these immunised mice. 
      CONCLUSION: MTX can function as a potent adjuvant in DC vaccines by increasing 
      antigen presentation and T cell priming. Our findings provide a new strategy for 
      the application of DC-based anti-tumour immunotherapy.
CI  - (c) The Author(s), 2021.
FAU - Shi, Gao-Na
AU  - Shi GN
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union 
      Medical College, Beijing, China.
FAU - Hu, Min
AU  - Hu M
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union 
      Medical College, Beijing, China.
FAU - Chen, Chengjuan
AU  - Chen C
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union 
      Medical College, Beijing, China.
FAU - Fu, Junmin
AU  - Fu J
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union 
      Medical College, Beijing, China.
FAU - Shao, Shuai
AU  - Shao S
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union 
      Medical College, Beijing, China.
FAU - Zhou, Yu
AU  - Zhou Y
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union 
      Medical College, Beijing, China.
FAU - Wu, Lei
AU  - Wu L
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union 
      Medical College, Beijing, China.
FAU - Zhang, Tiantai
AU  - Zhang T
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union 
      Medical College, Room 216, Beijing, 100050, China.
LA  - eng
PT  - Journal Article
DEP - 20210121
PL  - England
TA  - Ther Adv Med Oncol
JT  - Therapeutic advances in medical oncology
JID - 101510808
PMC - PMC7841859
OTO - NOTNLM
OT  - IFN-gamma releasing CD8+ T cells
OT  - NLRP3 inflammasome
OT  - antigen presentation
OT  - dendritic cells
OT  - methotrexate
COIS- Conflict of interest statement: The authors declare that there is no conflict of 
      interest.
EDAT- 2021/02/23 06:00
MHDA- 2021/02/23 06:01
PMCR- 2021/01/21
CRDT- 2021/02/22 05:54
PHST- 2020/02/13 00:00 [received]
PHST- 2020/12/17 00:00 [accepted]
PHST- 2021/02/22 05:54 [entrez]
PHST- 2021/02/23 06:00 [pubmed]
PHST- 2021/02/23 06:01 [medline]
PHST- 2021/01/21 00:00 [pmc-release]
AID - 10.1177_1758835920987056 [pii]
AID - 10.1177/1758835920987056 [doi]
PST - epublish
SO  - Ther Adv Med Oncol. 2021 Jan 21;13:1758835920987056. doi: 
      10.1177/1758835920987056. eCollection 2021.