PMID- 30674537
OWN - NLM
STAT- In-Data-Review
LR  - 20190329
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Linking)
VI  - 79
IP  - 6
DP  - 2019 Mar 15
TI  - Loss of E-Cadherin Inhibits CD103 Antitumor Activity and Reduces Checkpoint
      Blockade Responsiveness in Melanoma.
PG  - 1113-1123
LID - 10.1158/0008-5472.CAN-18-1722 [doi]
AB  - Identifying controlling features of responsiveness to checkpoint blockade
      therapies is an urgent goal in oncology research. Our group and others have
      previously shown melanoma tumors resistant to checkpoint blockade display
      features of mesenchymal transition, including E-cadherin loss. Here, we present
      the first in vivo evidence that E-cadherin from tumor cells facilitate immune
      attack, using a B16F10 melanoma mouse model in which E-cadherin is exogenously
      expressed (B16.Ecad). We find, compared with vector control, B16.Ecad exhibits
      delayed tumor growth, reduced metastatic potential, and increased overall
      survival in vivo. Transplantation of B16.Ecad into Rag1(-/-) and CD103(-/-) mice 
      abrogated the tumor growth delay. This indicates the anti-melanoma response
      against B16.Ecad is both immune and CD103(+) mediated. Moreover, B16.Ecad showed 
      increased responsiveness to combination immune checkpoint blockade (ICB) compared
      with vector control. This work establishes a rationale for ICB responses observed
      in high E-cadherin-expressing tumors and suggests therapeutic advancement through
      amplifying CD103(+) immune cell subsets.Significance: These findings identify the
      mechanism behind checkpoint blockade resistance observed in melanoma that has
      undergone mesenchymal transition and suggest activation of CD103(+) immune cells 
      as a therapeutic strategy against other E-cadherin-expressing
      malignancies.Graphical Abstract:
      http://cancerres.aacrjournals.org/content/canres/79/6/1113/F1.large.jpg.
CI  - (c)2019 American Association for Cancer Research.
FAU - Shields, Bradley D
AU  - Shields BD
AD  - Department of Biochemistry and Molecular Biology, University of Arkansas for
      Medical Sciences, Little Rock, Arkansas.
FAU - Koss, Brian
AU  - Koss B
AD  - Department of Biochemistry and Molecular Biology, University of Arkansas for
      Medical Sciences, Little Rock, Arkansas.
FAU - Taylor, Erin M
AU  - Taylor EM
AD  - Department of Biochemistry and Molecular Biology, University of Arkansas for
      Medical Sciences, Little Rock, Arkansas.
FAU - Storey, Aaron J
AU  - Storey AJ
AD  - Department of Biochemistry and Molecular Biology, University of Arkansas for
      Medical Sciences, Little Rock, Arkansas.
FAU - West, Kirk L
AU  - West KL
AUID- ORCID: https://orcid.org/0000-0002-9894-4549
AD  - Department of Biochemistry and Molecular Biology, University of Arkansas for
      Medical Sciences, Little Rock, Arkansas.
FAU - Byrum, Stephanie D
AU  - Byrum SD
AD  - Department of Biochemistry and Molecular Biology, University of Arkansas for
      Medical Sciences, Little Rock, Arkansas.
AD  - Arkansas Children's Research Institute, Little Rock, Arkansas.
FAU - Mackintosh, Samuel G
AU  - Mackintosh SG
AD  - Department of Biochemistry and Molecular Biology, University of Arkansas for
      Medical Sciences, Little Rock, Arkansas.
FAU - Edmondson, Rick
AU  - Edmondson R
AD  - College of Medicine, University of Arkansas for Medical Sciences, Little Rock,
      Arkansas.
FAU - Mahmoud, Fade
AU  - Mahmoud F
AUID- ORCID: https://orcid.org/0000-0002-1662-1640
AD  - College of Medicine, University of Arkansas for Medical Sciences, Little Rock,
      Arkansas.
FAU - Shalin, Sara C
AU  - Shalin SC
AUID- ORCID: https://orcid.org/0000-0001-5445-3783
AD  - Department of Pathology, University of Arkansas for Medical Sciences, Little
      Rock, Arkansas.
FAU - Tackett, Alan J
AU  - Tackett AJ
AD  - Department of Biochemistry and Molecular Biology, University of Arkansas for
      Medical Sciences, Little Rock, Arkansas. ajtackett@uams.edu.
AD  - Arkansas Children's Research Institute, Little Rock, Arkansas.
LA  - eng
GR  - UL1 TR000039/TR/NCATS NIH HHS/United States
GR  - P20 GM103429/GM/NIGMS NIH HHS/United States
GR  - P20 GM121293/GM/NIGMS NIH HHS/United States
GR  - S10 OD018445/OD/NIH HHS/United States
GR  - P20 GM103625/GM/NIGMS NIH HHS/United States
PT  - Journal Article
DEP - 20190123
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
PMC - PMC6420873
MID - NIHMS1519706
EDAT- 2019/01/25 06:00
MHDA- 2019/01/25 06:00
CRDT- 2019/01/25 06:00
PMCR- 2020/03/15 00:00
PHST- 2018/06/07 00:00 [received]
PHST- 2018/11/04 00:00 [revised]
PHST- 2019/01/18 00:00 [accepted]
PHST- 2020/03/15 00:00 [pmc-release]
PHST- 2019/01/25 06:00 [pubmed]
PHST- 2019/01/25 06:00 [medline]
PHST- 2019/01/25 06:00 [entrez]
AID - 0008-5472.CAN-18-1722 [pii]
AID - 10.1158/0008-5472.CAN-18-1722 [doi]
PST - ppublish
SO  - Cancer Res. 2019 Mar 15;79(6):1113-1123. doi: 10.1158/0008-5472.CAN-18-1722. Epub
      2019 Jan 23.