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PMID: 28346412 Published · ppublish English Journal Article

VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer.

Nature medicine ·Vol. 23 ·No. 5 ·2017-05-00 ·Pages 551-555

Gao J, Ward JF, Pettaway CA, Shi LZ, Subudhi SK, Vence LM, Zhao H, Chen J, Chen H, Efstathiou E, Troncoso P, Allison JP, Logothetis CJ, Wistuba II, Sepulveda MA, Sun J, Wargo J, Blando J, Sharma P

Abstract

To date, anti-CTLA-4 (ipilimumab) or anti-PD-1 (nivolumab) monotherapy has not been demonstrated to be of substantial clinical benefit in patients with prostate cancer. To identify additional immune-inhibitory pathways in the prostate-tumor microenvironment, we evaluated untreated and ipilimumab-treated tumors from patients in a presurgical clinical trial. Levels of the PD-L1 and VISTA inhibitory molecules increased on independent subsets of macrophages in treated tumors. Our data suggest that VISTA represents another compensatory inhibitory pathway in prostate tumors after ipilimumab therapy.

MeSH Terms
Adenocarcinoma/drug therapy,immunology,metabolism Adult Aged Animals Antibodies, Monoclonal/therapeutic use Antineoplastic Agents/therapeutic use B7 Antigens/immunology,metabolism B7-H1 Antigen/immunology,metabolism Cell Line, Tumor Disease Models, Animal Flow Cytometry Fluorescent Antibody Technique Humans Immunohistochemistry In Vitro Techniques Ipilimumab Macrophages/immunology,metabolism Male Membrane Proteins/immunology,metabolism Mice Middle Aged Neoadjuvant Therapy Prostatectomy Prostatic Neoplasms/drug therapy,immunology,metabolism T-Lymphocytes Tissue Array Analysis
Chemicals
Antibodies, Monoclonal Antineoplastic Agents B7 Antigens B7-H1 Antigen CD274 protein, human Cd274 protein, mouse Ipilimumab Membrane Proteins VSIR protein, human Vsir protein, mouse
Authors & Affiliations
19 authors, click to expand affiliations / ORCID
Gao Jianjun
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Ward John F
Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Pettaway Curtis A
Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Shi Lewis Z
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Subudhi Sumit K
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Vence Luis M
The Immunotherapy Platform, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Zhao Hao
The Immunotherapy Platform, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Chen Jianfeng
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Chen Hong
The Immunotherapy Platform, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Efstathiou Eleni
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Troncoso Patricia
Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Allison James P
The Immunotherapy Platform, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. | Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Logothetis Christopher J
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Wistuba Ignacio I
Department of Translational Molecular Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Sepulveda Manuel A
Janssen Oncology Therapeutic Area, Janssen Research and Development, LLC, Pharmaceutical Companies of Johnson &Johnson, Spring House, Pennsylvania, USA.
Sun Jingjing
The Immunotherapy Platform, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Wargo Jennifer
Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Blando Jorge
The Immunotherapy Platform, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Sharma Padmanee
Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. | The Immunotherapy Platform, University of Texas MD Anderson Cancer Center, Houston, Texas, USA. | Department of Immunology, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
References (20)
20 references, click to expand
  1. Immune checkpoint targeting in cancer therapy: toward combination strategies with curative potential.
    Cell. 2015 Apr 9;161(2):205-14 PMID: 25860605
  2. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm.
    Nat Immunol. 2010 Oct;11(10):889-96 PMID: 20856220
  3. Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade.
    Cancer Discov. 2016 Aug;6(8):827-37 PMID: 27301722
  4. Increased frequency of ICOS+ CD4 T cells as a pharmacodynamic biomarker for anti-CTLA-4 therapy.
    Cancer Immunol Res. 2013 Oct;1(4):229-34 PMID: 24777852
  5. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
    N Engl J Med. 2012 Jun 28;366(26):2443-54 PMID: 22658127
  6. Anti-CTLA-4 therapy results in higher CD4+ICOShi T cell frequency and IFN-gamma levels in both nonmalignant and malignant prostate tissues.
    Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2729-34 PMID: 19202079
  7. Characterization of prostatic epithelial cell lines derived from transgenic adenocarcinoma of the mouse prostate (TRAMP) model.
    Cancer Res. 1997 Aug 15;57(16):3325-30 PMID: 9269988
  8. Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial.
    Clin Cancer Res. 2010 May 15;16(10 ):2861-71 PMID: 20460488
  9. VISTA is a novel broad-spectrum negative checkpoint regulator for cancer immunotherapy.
    Cancer Immunol Res. 2014 Jun;2(6):510-7 PMID: 24894088
  10. The future of immune checkpoint therapy.
    Science. 2015 Apr 3;348(6230):56-61 PMID: 25838373
  11. Clonal expansion of CD8 T cells in the systemic circulation precedes development of ipilimumab-induced toxicities.
    Proc Natl Acad Sci U S A. 2016 Oct 18;113(42):11919-11924 PMID: 27698113
  12. Multiplexed immunohistochemistry, imaging, and quantitation: a review, with an assessment of Tyramide signal amplification, multispectral imaging and multiplex analysis.
    Methods. 2014 Nov;70(1):46-58 PMID: 25242720
  13. Data-Driven Phenotypic Dissection of AML Reveals Progenitor-like Cells that Correlate with Prognosis.
    Cell. 2015 Jul 2;162(1):184-97 PMID: 26095251
  14. Review of immune-related adverse events in prostate cancer patients treated with ipilimumab: MD Anderson experience.
    Oncogene. 2015 Oct;34(43):5411-7 PMID: 25659583
  15. viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia.
    Nat Biotechnol. 2013 Jun;31(6):545-52 PMID: 23685480
  16. Interdependent IL-7 and IFN-γ signalling in T-cell controls tumour eradication by combined α-CTLA-4+α-PD-1 therapy.
    Nat Commun. 2016 Aug 08;7:12335 PMID: 27498556
  17. PD-L1 Expression Correlates with Tumor-Infiltrating Lymphocytes and Response to Neoadjuvant Chemotherapy in Breast Cancer.
    Cancer Immunol Res. 2015 Apr;3(4):326-32 PMID: 25527356
  18. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation.
    J Exp Med. 2000 Oct 2;192(7):1027-34 PMID: 11015443
  19. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial.
    Lancet Oncol. 2014 Jun;15(7):700-12 PMID: 24831977
  20. CTLA-4 blockade increases IFNgamma-producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients.
    Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):14987-92 PMID: 18818309
Article Info
Journal
Nature medicine
Abbr.
Nat Med
ISSN
1546-170X
DOI
10.1038/nm.4308
Published
2017-05-00
Epub
2017-00-27
Pages
551-555
Language
English
Region
United States
NLM ID
9502015
PMCID
PMC5466900
Subset
IM
Grants
NCI NIH HHS · K08 CA160692 · United States
NCI NIH HHS · R01 CA163793 · United States
NCI NIH HHS · P30 CA016672 · United States
NCATS NIH HHS · UL1 TR000371 · United States
NCI NIH HHS · K12 CA088084 · United States
NCI NIH HHS · P50 CA140388 · United States
External Links
PubMed source DOI: 10.1038/nm.4308 PMC Full Text View journal details
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