PMID- 28652246
OWN - NLM
STAT- MEDLINE
DCOM- 20171031
LR  - 20180412
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 77
IP  - 17
DP  - 2017 Sep 1
TI  - MAPK Signaling and Inflammation Link Melanoma Phenotype Switching to Induction of
      CD73 during Immunotherapy.
PG  - 4697-4709
LID - 10.1158/0008-5472.CAN-17-0395 [doi]
AB  - Evolution of tumor cell phenotypes promotes heterogeneity and therapy resistance.
      Here we found that induction of CD73, the enzyme that generates immunosuppressive
      adenosine, is linked to melanoma phenotype switching. Activating MAPK mutations
      and growth factors drove CD73 expression, which marked both nascent and full
      activation of a mesenchymal-like melanoma cell state program. Proinflammatory
      cytokines like TNFalpha cooperated with MAPK signaling through the c-Jun/AP-1
      transcription factor complex to activate CD73 transcription by binding to an
      intronic enhancer. In a mouse model of T-cell immunotherapy, CD73 was induced in 
      relapse melanomas, which acquired a mesenchymal-like phenotype. We also detected 
      CD73 upregulation in melanoma patients progressing under adoptive T-cell transfer
      or immune checkpoint blockade, arguing for an adaptive resistance mechanism. Our 
      work substantiates CD73 as a target to combine with current immunotherapies, but 
      its dynamic regulation suggests limited value of CD73 pretreatment expression as 
      a biomarker to stratify melanoma patients. Cancer Res; 77(17); 4697-709. (c)2017 
      AACR.
CI  - (c)2017 American Association for Cancer Research.
FAU - Reinhardt, Julia
AU  - Reinhardt J
AD  - Unit for RNA Biology, Department of Clinical Chemistry and Clinical Pharmacology,
      University of Bonn, Bonn, Germany.
FAU - Landsberg, Jennifer
AU  - Landsberg J
AD  - Laboratory of Experimental Dermatology, Department of Dermatology and Allergy,
      University of Bonn, Bonn, Germany.
AD  - Department of Dermatology, University Hospital Essen, West German Cancer Center, 
      University Duisburg-Essen, Essen, Germany.
FAU - Schmid-Burgk, Jonathan L
AU  - Schmid-Burgk JL
AD  - Institute of Molecular Medicine, University Hospital Bonn, University of Bonn,
      Bonn, Germany.
FAU - Ramis, Bartomeu Bibiloni
AU  - Ramis BB
AD  - Laboratory of Experimental Dermatology, Department of Dermatology and Allergy,
      University of Bonn, Bonn, Germany.
FAU - Bald, Tobias
AU  - Bald T
AD  - Laboratory of Experimental Dermatology, Department of Dermatology and Allergy,
      University of Bonn, Bonn, Germany.
AD  - Laboratory of Experimental Dermatology, Department of Dermatology, University of 
      Magdeburg, Magdeburg, Germany.
AD  - Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research
      Institute, Herston, Queensland, Australia.
FAU - Glodde, Nicole
AU  - Glodde N
AD  - Unit for RNA Biology, Department of Clinical Chemistry and Clinical Pharmacology,
      University of Bonn, Bonn, Germany.
AD  - Laboratory of Experimental Dermatology, Department of Dermatology and Allergy,
      University of Bonn, Bonn, Germany.
FAU - Lopez-Ramos, Dorys
AU  - Lopez-Ramos D
AD  - Laboratory of Experimental Dermatology, Department of Dermatology and Allergy,
      University of Bonn, Bonn, Germany.
AD  - Laboratory of Experimental Dermatology, Department of Dermatology, University of 
      Magdeburg, Magdeburg, Germany.
FAU - Young, Arabella
AU  - Young A
AD  - Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research
      Institute, Herston, Queensland, Australia.
AD  - School of Medicine, University of Queensland, Herston, Queensland, Australia.
FAU - Ngiow, Shin Foong
AU  - Ngiow SF
AD  - Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research
      Institute, Herston, Queensland, Australia.
AD  - School of Medicine, University of Queensland, Herston, Queensland, Australia.
FAU - Nettersheim, Daniel
AU  - Nettersheim D
AD  - Department of Developmental Pathology, Institute of Pathology, University of Bonn
      Medical School, Bonn, Germany.
FAU - Schorle, Hubert
AU  - Schorle H
AD  - Department of Developmental Pathology, Institute of Pathology, University of Bonn
      Medical School, Bonn, Germany.
FAU - Quast, Thomas
AU  - Quast T
AD  - Molecular Immunology and Cell Biology, Life and Medical Sciences Institute,
      University of Bonn, Bonn, Germany.
FAU - Kolanus, Waldemar
AU  - Kolanus W
AD  - Molecular Immunology and Cell Biology, Life and Medical Sciences Institute,
      University of Bonn, Bonn, Germany.
FAU - Schadendorf, Dirk
AU  - Schadendorf D
AD  - Department of Dermatology, University Hospital Essen, West German Cancer Center, 
      University Duisburg-Essen, Essen, Germany.
FAU - Long, Georgina V
AU  - Long GV
AD  - Melanoma Institute Australia and Sydney Medical School, The University of Sydney,
      Sydney, New South Wales, Australia.
FAU - Madore, Jason
AU  - Madore J
AD  - Melanoma Institute Australia and Sydney Medical School, The University of Sydney,
      Sydney, New South Wales, Australia.
FAU - Scolyer, Richard A
AU  - Scolyer RA
AD  - Melanoma Institute Australia and Sydney Medical School, The University of Sydney,
      Sydney, New South Wales, Australia.
AD  - Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred
      Hospital, Sydney, New South Wales, Australia.
FAU - Ribas, Antoni
AU  - Ribas A
AD  - University of California Los Angeles (UCLA), Los Angeles, California.
AD  - Jonsson Comprehensive Cancer Center, Los Angeles, California.
FAU - Smyth, Mark J
AU  - Smyth MJ
AD  - Immunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research
      Institute, Herston, Queensland, Australia.
AD  - School of Medicine, University of Queensland, Herston, Queensland, Australia.
FAU - Tumeh, Paul C
AU  - Tumeh PC
AD  - University of California Los Angeles (UCLA), Los Angeles, California.
AD  - Jonsson Comprehensive Cancer Center, Los Angeles, California.
FAU - Tuting, Thomas
AU  - Tuting T
AD  - Laboratory of Experimental Dermatology, Department of Dermatology and Allergy,
      University of Bonn, Bonn, Germany.
AD  - Laboratory of Experimental Dermatology, Department of Dermatology, University of 
      Magdeburg, Magdeburg, Germany.
FAU - Holzel, Michael
AU  - Holzel M
AD  - Unit for RNA Biology, Department of Clinical Chemistry and Clinical Pharmacology,
      University of Bonn, Bonn, Germany. Michael.Hoelzel@ukb.uni-bonn.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170626
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (Transcription Factor AP-1)
RN  - EC 2.7.11.24 (MAPK1 protein, human)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 3.1.3.5 (5'-Nucleotidase)
RN  - EC 3.1.3.5 (NT5E protein, human)
RN  - K72T3FS567 (Adenosine)
SB  - IM
MH  - 5'-Nucleotidase/*metabolism
MH  - Adenosine/metabolism
MH  - Adoptive Transfer
MH  - Animals
MH  - GPI-Linked Proteins/metabolism
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - *Immunotherapy
MH  - Inflammation/*complications/pathology
MH  - Melanoma/immunology/metabolism/*pathology/therapy
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitogen-Activated Protein Kinase 1/*metabolism
MH  - Neoplasm Invasiveness
MH  - Prognosis
MH  - Retrospective Studies
MH  - T-Lymphocytes/*transplantation
MH  - Transcription Factor AP-1/metabolism
MH  - Tumor Cells, Cultured
EDAT- 2017/06/28 06:00
MHDA- 2017/11/01 06:00
CRDT- 2017/06/28 06:00
PHST- 2017/02/11 00:00 [received]
PHST- 2017/05/13 00:00 [revised]
PHST- 2017/06/20 00:00 [accepted]
PHST- 2017/06/28 06:00 [pubmed]
PHST- 2017/11/01 06:00 [medline]
PHST- 2017/06/28 06:00 [entrez]
AID - 0008-5472.CAN-17-0395 [pii]
AID - 10.1158/0008-5472.CAN-17-0395 [doi]
PST - ppublish
SO  - Cancer Res. 2017 Sep 1;77(17):4697-4709. doi: 10.1158/0008-5472.CAN-17-0395. Epub
      2017 Jun 26.