GITR ligation enhances functionality of tumor-infiltrating T cells in hepatocellular carcinoma.


Journal

International journal of cancer
ISSN: 1097-0215
Titre abrégé: Int J Cancer
Pays: United States
ID NLM: 0042124

Informations de publication

Date de publication:
15 08 2019
Historique:
received: 12 09 2018
revised: 09 01 2019
accepted: 14 01 2019
pubmed: 6 2 2019
medline: 4 12 2019
entrez: 6 2 2019
Statut: ppublish

Résumé

No curative treatment options are available for advanced hepatocellular carcinoma (HCC). Anti-PD1 antibody therapy can induce tumor regression in 20% of advanced HCC patients, demonstrating that co-inhibitory immune checkpoint blockade has therapeutic potential for this type of cancer. However, whether agonistic targeting of co-stimulatory receptors might be able to stimulate anti-tumor immunity in HCC is as yet unknown. We investigated whether agonistic targeting of the co-stimulatory receptor GITR could reinvigorate ex vivo functional responses of tumor-infiltrating lymphocytes (TIL) freshly isolated from resected tumors of HCC patients. In addition, we compared GITR expression between TIL and paired samples of leukocytes isolated from blood and tumor-free liver tissues, and studied the effects of combined GITR and PD1 targeting on ex vivo TIL responses. In all three tissue compartments, CD4

Identifiants

pubmed: 30719701
doi: 10.1002/ijc.32181
pmc: PMC6619339
doi:

Substances chimiques

Antibodies, Monoclonal 0
Glucocorticoid-Induced TNFR-Related Protein 0
RNA, Messenger 0
TNFRSF18 protein, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1111-1124

Informations de copyright

© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

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Auteurs

Adriaan A van Beek (AA)

Departments of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

Guoying Zhou (G)

Departments of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

Michail Doukas (M)

Department of Pathology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

Patrick P C Boor (PPC)

Departments of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

Lisanne Noordam (L)

Departments of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

Shanta Mancham (S)

Departments of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

Lucia Campos Carrascosa (L)

Departments of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

Marieke van der Heide-Mulder (M)

Departments of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

Wojciech G Polak (WG)

Department of Surgery, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

Jan N M Ijzermans (JNM)

Department of Surgery, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

Qiuwei Pan (Q)

Departments of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

Carlo Heirman (C)

Laboratory of Molecular and Cellular Therapy, Vrije Universiteit Brussel, Brussels, Belgium.

Ashley Mahne (A)

Cancer Immunology Discovery Unit, Pfizer Inc., South San Francisco, CA.

Samantha L Bucktrout (SL)

Cancer Immunology Discovery Unit, Pfizer Inc., South San Francisco, CA.

Marco J Bruno (MJ)

Departments of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

Dave Sprengers (D)

Departments of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

Jaap Kwekkeboom (J)

Departments of Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, The Netherlands.

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Classifications MeSH