PMID- 37584709
OWN - NLM
STAT- MEDLINE
DCOM- 20231027
LR  - 20231027
IS  - 1432-1335 (Electronic)
IS  - 0171-5216 (Linking)
VI  - 149
IP  - 16
DP  - 2023 Nov
TI  - PTPN3 inhibition contributes to the activation of the dendritic cell function to 
      be a promising new immunotherapy target.
PG  - 14619-14630
LID - 10.1007/s00432-023-05250-8 [doi]
AB  - PURPOSE: In a previous study, protein tyrosine phosphatase non-receptor type 
      (PTPN) 3 was identified as an immune checkpoint molecule in lymphocytes, and its 
      potential as a novel target for cancer immunotherapy was anticipated. However, 
      evaluation of dendritic cell (DC) function as antigen-presenting cells is 
      critical for the development of immunotherapy. In this study, we aimed to analyze 
      the biological effect of PTPN3 on DCs induced from human peripheral blood 
      monocytes obtained from healthy individuals. METHODS: We used short-interfering 
      RNA to knock down PTP3 in DCs. For DC maturation, we added cancer cell lysate and 
      tumor necrosis factor-alpha/interferon-alpha to immature DCs. In the cytotoxic assay, the 
      target cancer cells were SBC5, unmatched with DCs from healthy human leukocyte 
      antigen (HLA)-A24, or Sq-1, matched with DCs. Enzyme-linked immunosorbent assay 
      was used to determine the amount of cytokines. To examine the intracellular 
      signaling system, intracellular staining was used. RESULTS: PTPN3 knockdown 
      significantly increased the number of DCs, expression of CD80 and chemokine 
      receptor (CCR)7, and production of interleukin-12p40/p70 in mature DCs. In the 
      HLA-A24-restricted DC and human lung squamous cell carcinoma cell cytotoxic 
      assay, inhibition of PTPN3 expression in mature DCs induced cytotoxic T 
      lymphocytes with increased production of INF-gamma and granzyme B, and enhanced 
      toxicity against cancer cells and migration to cancer. Furthermore, inhibition of 
      PTPN3 expression activated the mitogen-activated protein kinase pathway in DCs. 
      CONCLUSION: Based on our findings, inhibition of PTPN3 expression could 
      contribute to the development of novel cancer immunotherapies that activate not 
      only lymphocytes but also DCs.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
      part of Springer Nature.
FAU - Iwamoto, Naoya
AU  - Iwamoto N
AD  - Department of Cancer Therapy and Research, Graduate School of Medical Sciences, 
      Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
FAU - Onishi, Hideya
AU  - Onishi H
AD  - Department of Cancer Therapy and Research, Graduate School of Medical Sciences, 
      Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan. 
      ohnishi.hideya.928@m.kyushu-u.ac.jp.
FAU - Masuda, Shogo
AU  - Masuda S
AD  - Department of Cancer Therapy and Research, Graduate School of Medical Sciences, 
      Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
FAU - Imaizumi, Akira
AU  - Imaizumi A
AD  - Department of Cancer Therapy and Research, Graduate School of Medical Sciences, 
      Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
FAU - Sakanashi, Keita
AU  - Sakanashi K
AD  - Department of Cancer Therapy and Research, Graduate School of Medical Sciences, 
      Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
FAU - Morisaki, Shinji
AU  - Morisaki S
AD  - Department of Cancer Therapy and Research, Graduate School of Medical Sciences, 
      Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
FAU - Nagao, Shinjiro
AU  - Nagao S
AD  - Department of Cancer Therapy and Research, Graduate School of Medical Sciences, 
      Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
FAU - Koga, Satoko
AU  - Koga S
AD  - Department of Cancer Therapy and Research, Graduate School of Medical Sciences, 
      Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
FAU - Ozono, Keigo
AU  - Ozono K
AD  - Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Umebayashi, Masayo
AU  - Umebayashi M
AD  - Fukuoka General Cancer Clinic, Fukuoka, 812-0018, Japan.
FAU - Morisaki, Takashi
AU  - Morisaki T
AD  - Fukuoka General Cancer Clinic, Fukuoka, 812-0018, Japan.
FAU - Nakamura, Masafumi
AU  - Nakamura M
AD  - Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
LA  - eng
PT  - Journal Article
DEP - 20230816
PL  - Germany
TA  - J Cancer Res Clin Oncol
JT  - Journal of cancer research and clinical oncology
JID - 7902060
RN  - 0 (Cytokines)
RN  - 0 (Interleukins)
RN  - EC 3.1.3.48 (PTPN3 protein, human)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 3)
SB  - IM
MH  - Humans
MH  - *Dendritic Cells
MH  - Cytokines/metabolism
MH  - T-Lymphocytes, Cytotoxic
MH  - Interleukins
MH  - *Neoplasms/metabolism
MH  - Immunotherapy
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 3/metabolism
OTO - NOTNLM
OT  - Anticancer immunotherapy
OT  - Immune checkpoint
OT  - MAPK pathway
OT  - Mature dendritic cell
OT  - PTPN3
EDAT- 2023/08/16 12:42
MHDA- 2023/10/27 06:43
CRDT- 2023/08/16 11:05
PHST- 2023/06/24 00:00 [received]
PHST- 2023/08/04 00:00 [accepted]
PHST- 2023/10/27 06:43 [medline]
PHST- 2023/08/16 12:42 [pubmed]
PHST- 2023/08/16 11:05 [entrez]
AID - 10.1007/s00432-023-05250-8 [pii]
AID - 10.1007/s00432-023-05250-8 [doi]
PST - ppublish
SO  - J Cancer Res Clin Oncol. 2023 Nov;149(16):14619-14630. doi: 
      10.1007/s00432-023-05250-8. Epub 2023 Aug 16.