PMID- 37901221
OWN - NLM
STAT- MEDLINE
DCOM- 20231031
LR  - 20231106
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - An optimized cocktail of small molecule inhibitors promotes the maturation of 
      dendritic cells in GM-CSF mouse bone marrow culture.
PG  - 1264609
LID - 10.3389/fimmu.2023.1264609 [doi]
LID - 1264609
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells, playing an 
      essential role in the pathogen and tumor recognition, and anti-tumor immunity, 
      and linking both the innate and adaptive immunity. The monocyte-derived DCs 
      generated by ex vivo culture, have been used for cancer immunotherapy to 
      eliminate tumor; however, the clinical efficacies are not sufficient, and further 
      improvement is essential. In this study, we established a method to generate DCs 
      using small molecule compounds for cancer immunotherapy. We observed an increase 
      in the percentage of CD11c(+)I-A/I-E(high) cells, representing DCs, by adding 
      four small molecular inhibitors: Y27632, PD0325901, PD173074, and PD98059 
      (abbreviated as YPPP), in mouse bone marrow (BM) culture with 
      granulocyte-macrophage colony stimulating factor (GM-CSF). BM-derived DCs 
      cultured with YPPP (YPPP-DCs) showed high responsiveness to lipopolysaccharide 
      stimulation, resulting in increased interleukin (IL) -12 production and enhanced 
      proliferation activity when co-cultured with naive T cells compared with the 
      vehicle control. RNA-seq analysis revealed an upregulation of peroxisome 
      proliferator - activated receptor (PPAR) gamma associated genes increased in 
      YPPP-DCs. In tumor models treated with anti-programmed death (PD) -1 therapies, 
      mice injected intratumorally with YPPP-DCs as a DCs vaccine exhibited reduced 
      tumor growth and increased survival. These findings suggested that our method 
      would be useful for the induction of DCs that efficiently activate effector T 
      cells for cancer immunotherapy.
CI  - Copyright (c) 2023 Matsuba, Ura, Saito, Ogasawara, Shimodaira, Niida and Onai.
FAU - Matsuba, Shintaro
AU  - Matsuba S
AD  - Department of Immunology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
FAU - Ura, Hiroki
AU  - Ura H
AD  - Center for Clinical Genomics, Kanazawa Medical University Hospital, Uchinada, 
      Ishikawa, Japan.
AD  - Division of Genomic Medicine, Department of Advanced Medicine, Medical Research 
      Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
FAU - Saito, Fumiji
AU  - Saito F
AD  - Department of Immunology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
FAU - Ogasawara, Chie
AU  - Ogasawara C
AD  - Department of Immunology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
FAU - Shimodaira, Shigetaka
AU  - Shimodaira S
AD  - Department of Regenerative Medicine, Kanazawa Medical University, Uchinada, 
      Ishikawa, Japan.
AD  - Center for Regenerative Medicine, Kanazawa Medical University Hospital, Uchinada, 
      Ishikawa, Japan.
FAU - Niida, Yo
AU  - Niida Y
AD  - Center for Clinical Genomics, Kanazawa Medical University Hospital, Uchinada, 
      Ishikawa, Japan.
AD  - Division of Genomic Medicine, Department of Advanced Medicine, Medical Research 
      Institute, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
FAU - Onai, Nobuyuki
AU  - Onai N
AD  - Department of Immunology, Kanazawa Medical University, Uchinada, Ishikawa, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231013
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology
MH  - Dendritic Cells
MH  - Bone Marrow
MH  - T-Lymphocytes
MH  - *Neoplasms
PMC - PMC10611476
OTO - NOTNLM
OT  - cytokine production
OT  - dendritic cells
OT  - immunotherapy
OT  - mixed lymphoid reaction
OT  - small molecule inhibitor
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest. The author(s) declared that they were an editorial board 
      member of Frontiers, at the time of submission. This had no impact on the peer 
      review process and the final decision.
EDAT- 2023/10/30 06:47
MHDA- 2023/10/31 06:42
PMCR- 2023/01/01
CRDT- 2023/10/30 04:47
PHST- 2023/07/21 00:00 [received]
PHST- 2023/09/21 00:00 [accepted]
PHST- 2023/10/31 06:42 [medline]
PHST- 2023/10/30 06:47 [pubmed]
PHST- 2023/10/30 04:47 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1264609 [doi]
PST - epublish
SO  - Front Immunol. 2023 Oct 13;14:1264609. doi: 10.3389/fimmu.2023.1264609. 
      eCollection 2023.