PMID- 30635425
OWN - NLM
STAT- MEDLINE
DCOM- 20190322
LR  - 20190401
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 116
IP  - 5
DP  - 2019 Jan 29
TI  - Comparison of immune infiltrates in melanoma and pancreatic cancer highlights
      VISTA as a potential target in pancreatic cancer.
PG  - 1692-1697
LID - 10.1073/pnas.1811067116 [doi]
AB  - Immune checkpoint therapy (ICT) has transformed cancer treatment in recent years;
      however, treatment response is not uniform across tumor types. The tumor immune
      microenvironment plays a critical role in determining response to ICT; therefore,
      understanding the differential immune infiltration between ICT-sensitive and
      ICT-resistant tumor types will help to develop effective treatment strategies. We
      performed a comprehensive analysis of the immune tumor microenvironment of an
      ICT-sensitive tumor (melanoma, n = 44) and an ICT-resistant tumor (pancreatic
      cancer, n = 67). We found that a pancreatic tumor has minimal to moderate
      infiltration of CD3, CD4, and CD8 T cells; however, the immune infiltrates are
      predominantly present in the stromal area of the tumor and are excluded from
      tumoral area compared with melanoma, where the immune infiltrates are primarily
      present in the tumoral area. Metastatic pancreatic ductal adenocarcinomas (PDACs)
      had a lower infiltration of total T cells compared with resectable primary PDACs,
      suggesting that metastatic PDACs have poor immunogenicity. Further, a
      significantly higher number of CD68(+) macrophages and VISTA(+) cells (also known
      as V-domain immunoglobulin suppressor of T cell activation) were found in the
      pancreatic stromal area compared with melanoma. We identified VISTA as a potent
      inhibitory checkpoint that is predominantly expressed on CD68+ macrophages on
      PDACs. These data suggest that VISTA may be a relevant immunotherapy target for
      effective treatment of patients with pancreatic cancer.
FAU - Blando, Jorge
AU  - Blando J
AD  - The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center,
      Houston, TX 77054.
FAU - Sharma, Anu
AU  - Sharma A
AD  - Department of Genitourinary Medical Oncology, The University of Texas MD Anderson
      Cancer Center, Houston, TX 77030.
FAU - Higa, Maria Gisela
AU  - Higa MG
AD  - The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center,
      Houston, TX 77054.
FAU - Zhao, Hao
AU  - Zhao H
AD  - The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center,
      Houston, TX 77054.
FAU - Vence, Luis
AU  - Vence L
AD  - The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center,
      Houston, TX 77054.
FAU - Yadav, Shalini S
AU  - Yadav SS
AD  - The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center,
      Houston, TX 77054.
FAU - Kim, Jiseong
AU  - Kim J
AD  - The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center,
      Houston, TX 77054.
FAU - Sepulveda, Alejandro M
AU  - Sepulveda AM
AD  - Janssen Oncology Therapeutic Area, Janssen Research and Development, LLC,
      Pharmaceutical Companies of Johnson & Johnson, Spring House, PA 19477.
FAU - Sharp, Michael
AU  - Sharp M
AD  - Janssen Oncology Therapeutic Area, Janssen Research and Development, LLC,
      Pharmaceutical Companies of Johnson & Johnson, Spring House, PA 19477.
FAU - Maitra, Anirban
AU  - Maitra A
AD  - Department of Pathology, The University of Texas MD Anderson Cancer Center,
      Houston, TX 77030.
AD  - Department of Translational Molecular Pathology, The University of Texas MD
      Anderson Cancer Center, Houston, TX 77030.
FAU - Wargo, Jennifer
AU  - Wargo J
AD  - Department of Surgical Oncology, The University of Texas MD Anderson Cancer
      Center, Houston, TX 77030.
FAU - Tetzlaff, Michael
AU  - Tetzlaff M
AD  - Department of Pathology, The University of Texas MD Anderson Cancer Center,
      Houston, TX 77030.
FAU - Broaddus, Russell
AU  - Broaddus R
AD  - Department of Pathology, The University of Texas MD Anderson Cancer Center,
      Houston, TX 77030.
FAU - Katz, Matthew H G
AU  - Katz MHG
AD  - Department of Surgical Oncology, The University of Texas MD Anderson Cancer
      Center, Houston, TX 77030.
FAU - Varadhachary, Gauri R
AU  - Varadhachary GR
AD  - Department of Gastrointestinal Medical Oncology, The University of Texas MD
      Anderson Cancer Center, Houston, TX 77030.
FAU - Overman, Michael
AU  - Overman M
AD  - Department of Gastrointestinal Medical Oncology, The University of Texas MD
      Anderson Cancer Center, Houston, TX 77030.
FAU - Wang, Huamin
AU  - Wang H
AD  - Department of Pathology, The University of Texas MD Anderson Cancer Center,
      Houston, TX 77030.
FAU - Yee, Cassian
AU  - Yee C
AD  - Department of Melanoma Medical Oncology, The University of Texas MD Anderson
      Cancer Center, Houston, TX 77030.
FAU - Bernatchez, Chantale
AU  - Bernatchez C
AD  - Department of Melanoma Medical Oncology, The University of Texas MD Anderson
      Cancer Center, Houston, TX 77030.
FAU - Iacobuzio-Donahue, Christine
AU  - Iacobuzio-Donahue C
AD  - David Rubenstein Pancreatic Cancer Research Center, Memorial Sloan Kettering
      Cancer Center, New York, NY 10065.
FAU - Basu, Sreyashi
AU  - Basu S
AD  - The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center,
      Houston, TX 77054.
FAU - Allison, James P
AU  - Allison JP
AD  - The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center,
      Houston, TX 77054; jallison@mdanderson.org padsharma@mdanderson.org.
AD  - Department of Immunology, The University of Texas MD Anderson Cancer Center,
      Houston, TX 77030.
FAU - Sharma, Padmanee
AU  - Sharma P
AD  - The Immunotherapy Platform, The University of Texas MD Anderson Cancer Center,
      Houston, TX 77054; jallison@mdanderson.org padsharma@mdanderson.org.
AD  - Department of Genitourinary Medical Oncology, The University of Texas MD Anderson
      Cancer Center, Houston, TX 77030.
AD  - Department of Immunology, The University of Texas MD Anderson Cancer Center,
      Houston, TX 77030.
LA  - eng
GR  - R01 CA163793/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190111
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (B7 Antigens)
RN  - 0 (VSIR protein, human)
SB  - IM
MH  - Adenocarcinoma/metabolism
MH  - B7 Antigens/*metabolism
MH  - CD8-Positive T-Lymphocytes/metabolism
MH  - Carcinoma, Pancreatic Ductal/metabolism
MH  - Humans
MH  - Immunotherapy/methods
MH  - Lymphocyte Activation/physiology
MH  - Lymphocytes, Tumor-Infiltrating/*metabolism
MH  - Melanoma/*metabolism
MH  - Pancreatic Neoplasms/*metabolism
MH  - Tumor Microenvironment/physiology
PMC - PMC6358697
OTO - NOTNLM
OT  - *immune checkpoints
OT  - *immune infiltrate
OT  - *immune monitoring
OT  - *immunopathology
OT  - *pancreatic cancer
COIS- Conflict of interest statement: J.P.A. is an inventor and recipient of royalties 
      from intellectual property licensed to Bristol-Meyer Squibb, Merck, and Jounce.
      He is a member of the scientific advisory board for Jounce Therapeutics, Neon
      Therapeutics, Amgen, Apricity, BioAlta, Forty-Seven, Tvardi Therapeutics,
      TapImmune, ImaginAB, Codiak Biosciences, and Marker Therapeutics. J.P.A. and P.S.
      own a patent licensed to Jounce Therapeutics. P.S. serves as a consultant for
      Constellation, Jounce Therapuetics, Kite Pharma, Neon Therapeutics, BioAtla,
      Pieris Pharmaceuticals, Oncolytics Biotech, Merck, BioMx, Forty-Seven, Polaris,
      Apricity, Marker Therapeutics, Codiak, ImaginAB, and TapImmune. She also has
      stock ownership in Jounce, Neon Therapeutics, Constellation, Oncolytics,
      BioAtlanta, Forty-Seven, Apricity, Polaris, Marker Therapeutics, Codiak,
      ImaginAB, and TapImmune. A.S. is an employee of Janssen.
EDAT- 2019/01/13 06:00
MHDA- 2019/03/23 06:00
CRDT- 2019/01/13 06:00
PMCR- 2019/07/29 00:00
PHST- 2019/07/29 00:00 [pmc-release]
PHST- 2019/01/13 06:00 [pubmed]
PHST- 2019/03/23 06:00 [medline]
PHST- 2019/01/13 06:00 [entrez]
AID - 1811067116 [pii]
AID - 10.1073/pnas.1811067116 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1692-1697. doi:
      10.1073/pnas.1811067116. Epub 2019 Jan 11.