Targeting PIM Kinase with PD1 Inhibition Improves Immunotherapeutic Antitumor T-cell Response.

Animals Antibodies / immunology Biphenyl Compounds / pharmacology Cell Line, Tumor Humans Immunotherapy, Adoptive / methods Mice, Inbred C57BL Mice, Knockout Neoplasms, Experimental / immunology Programmed Cell Death 1 Receptor / antagonists & inhibitors Protein Kinase Inhibitors / pharmacology Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors T-Lymphocytes / immunology Thiazolidines / pharmacology Treatment Outcome Xenograft Model Antitumor Assays / methods

Journal

Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500

Informations de publication

Date de publication:
01 02 2019
Historique:
received: 02 03 2018
revised: 29 06 2018
accepted: 10 10 2018
pubmed: 18 10 2018
medline: 14 4 2020
entrez: 18 10 2018
Statut: ppublish

Résumé

Adoptive T-cell therapy (ACT) of cancer, which involves the infusion of The role of PIM kinases in T cells was studied either by genetic ablation (PIM1 With inhibition of PIM kinases, T cells had significant reduction in their uptake of glucose, and upregulated expression of memory-associated genes that inversely correlate with glycolysis. In addition, the expression of CD38, which negatively regulates the metabolic fitness of the T cells, was also reduced in PimKi-treated cells. Importantly, the efficacy of antitumor T-cell therapy was markedly improved by inhibiting PIM kinases in tumor-bearing mice receiving ACT, and further enhanced by adding anti-PD1 antibody to this combination. This study highlights the potential therapeutic significance of combinatorial strategies where ACT and inhibition of signaling kinase with checkpoint blockade could improve tumor control.

Identifiants

DOI: 10.1158/1078-0432.CCR-18-0706 PMID: 30327305 PMC: PMC6361669
pubmed: 30327305
pii: 1078-0432.CCR-18-0706
doi: 10.1158/1078-0432.CCR-18-0706
pmc: PMC6361669
mid: NIHMS1509933
doi:

Substances chimiques

AZD1208 0
Antibodies 0
Biphenyl Compounds 0
Programmed Cell Death 1 Receptor 0
Protein Kinase Inhibitors 0
Thiazolidines 0
Proto-Oncogene Proteins c-pim-1 EC 2.7.11.1
proto-oncogene proteins pim EC 2.7.11.1

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

IM

Pagination

1036-1049

Subventions

Organisme : NCI NIH HHS
ID : R01 CA173200
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA023074
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA137725
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA138930
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA138313
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103542
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA198646
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA203628
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA154778
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA217987
Pays : United States

Informations de copyright

©2018 American Association for Cancer Research.

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Auteurs

Shilpak Chatterjee (S)

Department of Surgery, Medical University of South Carolina, Charleston, South Carolina.

Paramita Chakraborty (P)

Department of Surgery, Medical University of South Carolina, Charleston, South Carolina.

Anusara Daenthanasanmak (A)

Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, South Carolina.

Supinya Iamsawat (S)

Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, South Carolina.

Gabriela Andrejeva (G)

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.

Libia A Luevano (LA)

University of Arizona Cancer Center, University of Arizona, Tucson, Arizona.

Melissa Wolf (M)

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.

Uday Baliga (U)

Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina.
ORCID: 0000-0002-4557-8645

Carsten Krieg (C)

Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, South Carolina.

Craig C Beeson (CC)

Department of Pharmaceutical and Biomedical Sciences, Medical University of South Carolina, Charleston, South Carolina.

Meenal Mehrotra (M)

Department of Pathology & Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina.

Elizabeth G Hill (EG)

Department of Public Health, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina.

Jeffery C Rathmell (JC)

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.

Xue-Zhong Yu (XZ)

Department of Microbiology & Immunology, Medical University of South Carolina, Charleston, South Carolina.

Andrew S Kraft (AS)

University of Arizona Cancer Center, University of Arizona, Tucson, Arizona.

Shikhar Mehrotra (S)

Department of Surgery, Medical University of South Carolina, Charleston, South Carolina. mehrotr@musc.edu.

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