PMID- 28680757
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210112
IS  - 2162-4011 (Print)
IS  - 2162-402X (Electronic)
IS  - 2162-4011 (Linking)
VI  - 6
IP  - 6
DP  - 2017
TI  - Downregulation of PTP1B and TC-PTP phosphatases potentiate dendritic cell-based 
      immunotherapy through IL-12/IFNgamma signaling.
PG  - e1321185
LID - 10.1080/2162402X.2017.1321185 [doi]
LID - e1321185
AB  - PTP1B and TC-PTP are highly related protein-tyrosine phosphatases (PTPs) that 
      regulate the JAK/STAT signaling cascade essential for cytokine-receptor 
      activation in immune cells. Here, we describe a novel immunotherapy approach 
      whereby monocyte-derived dendritic cell (moDC) function is enhanced by modulating 
      the enzymatic activities of PTP1B and TC-PTP. To downregulate or delete the 
      activity/expression of these PTPs, we generated mice with PTP-specific deletions 
      in the dendritic cell compartment or used PTP1B and TC-PTP specific inhibitor. 
      While total ablation of PTP1B or TC-PTP expression leads to tolerogenic DCs via 
      STAT3 hyperactivation, downregulation of either phosphatase remarkably shifts the 
      balance toward an immunogenic DC phenotype due to hyperactivation of STAT4, STAT1 
      and Src kinase. The resulting increase in IL-12 and IFNgamma production subsequently 
      amplifies the IL-12/STAT4/IFNgamma/STAT1/IL-12 positive autocrine loop and enhances 
      the therapeutic potential of mature moDCs in tumor-bearing mice. Furthermore, 
      pharmacological inhibition of both PTPs improves the maturation of defective 
      moDCs derived from pancreatic cancer (PaC) patients. Our study provides a new 
      advance in the use of DC-based cancer immunotherapy that is complementary to 
      current cancer therapeutics.
FAU - Penafuerte, Claudia
AU  - Penafuerte C
AD  - Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
FAU - Feldhammer, Matthew
AU  - Feldhammer M
AD  - Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
AD  - Department of Biochemistry, McGill University, Montreal, QC, Canada.
FAU - Mills, John R
AU  - Mills JR
AD  - Department of Biochemistry, McGill University, Montreal, QC, Canada.
FAU - Vinette, Valerie
AU  - Vinette V
AD  - Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
AD  - Department of Biochemistry, McGill University, Montreal, QC, Canada.
FAU - Pike, Kelly A
AU  - Pike KA
AD  - Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
FAU - Hall, Anita
AU  - Hall A
AD  - Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
AD  - McGill University Health Centre-Research Institute, MUHC-RI, Montreal, QC, 
      Canada.
FAU - Migon, Eva
AU  - Migon E
AD  - Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
FAU - Karsenty, Gerard
AU  - Karsenty G
AD  - Columbia University, New York, NY, USA.
FAU - Pelletier, Jerry
AU  - Pelletier J
AD  - Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
AD  - Department of Biochemistry, McGill University, Montreal, QC, Canada.
FAU - Zogopoulos, George
AU  - Zogopoulos G
AD  - Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
AD  - McGill University Health Centre-Research Institute, MUHC-RI, Montreal, QC, 
      Canada.
FAU - Tremblay, Michel L
AU  - Tremblay ML
AD  - Goodman Cancer Research Centre, McGill University, Montreal, QC, Canada.
AD  - Department of Biochemistry, McGill University, Montreal, QC, Canada.
LA  - eng
GR  - MOP-62887/CIHR/Canada
GR  - MOP- 361853/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170428
PL  - United States
TA  - Oncoimmunology
JT  - Oncoimmunology
JID - 101570526
PMC - PMC5486178
OTO - NOTNLM
OT  - Dendritic cells (DCs)
OT  - PTP1B
OT  - TC-PTP
OT  - immunotherapy
OT  - protein-tyrosine phosphatases
EDAT- 2017/07/07 06:00
MHDA- 2017/07/07 06:01
PMCR- 2017/04/28
CRDT- 2017/07/07 06:00
PHST- 2017/01/23 00:00 [received]
PHST- 2017/04/16 00:00 [revised]
PHST- 2017/04/17 00:00 [accepted]
PHST- 2017/07/07 06:00 [entrez]
PHST- 2017/07/07 06:00 [pubmed]
PHST- 2017/07/07 06:01 [medline]
PHST- 2017/04/28 00:00 [pmc-release]
AID - 1321185 [pii]
AID - 10.1080/2162402X.2017.1321185 [doi]
PST - epublish
SO  - Oncoimmunology. 2017 Apr 28;6(6):e1321185. doi: 10.1080/2162402X.2017.1321185. 
      eCollection 2017.