Journal article
Dual control of antitumor CD8 T cells through the programmed death-1/programmed death-ligand 1 pathway and immunosuppressive CD4 T cells: Regulation and counterregulation
The Journal of Immunology, Vol.183(12), pp.7898-7908
2009
Abstract
Tumors have evolved multiple mechanisms to evade immune destruction. One of these is expression of T cell inhibitory ligands such as programmed death-ligand 1 (PD-L1; B7-H1). In this study, we show that PD-L1 is highly expressed on mesothelioma tumor cells and within the tumor stroma. However, PD-L1 blockade only marginally affected tumor growth and was associated with the emergence of activated programmed death-1+ ICOS+ CD4 T cells in tumor-draining lymph nodes, whereas few activated CD8 T cells were present. Full activation of antitumor CD8 T cells, characterized as programmed death-1+ ICOS+ Ki-67+ and displaying CTL activity, was only observed when CD4 T cells were depleted, suggesting that a population of suppressive CD4 T cells exists. ICOS+ foxp3+ regulatory T cells were found to be regulated through PD-L1, identifying one potentially suppressive CD4 T cell population. Thus, PD-L1 blockade activates antitumor CD8 T cell most potently in the absence of CD4 T cells. These findings have implications for the development of PD-L1-based therapies.
Details
- Title
- Dual control of antitumor CD8 T cells through the programmed death-1/programmed death-ligand 1 pathway and immunosuppressive CD4 T cells: Regulation and counterregulation
- Authors/Creators
- A.J. Currie (Author/Creator) - The University of Western AustraliaA. Prosser (Author/Creator) - School of Medicine and PharmacologyA. McDonnell (Author/Creator) - School of Medicine and PharmacologyA.L. Cleaver (Author/Creator) - School of Medicine and PharmacologyB.W.S. Robinson (Author/Creator) - School of Medicine and PharmacologyG.J. Freeman (Author/Creator)R.G. van der Most (Author/Creator) - School of Medicine and Pharmacology
- Publication Details
- The Journal of Immunology, Vol.183(12), pp.7898-7908
- Publisher
- American Association of Immunologists
- Identifiers
- 991005541095507891
- Copyright
- © 2009 by The American Association of Immunologists, I
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
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- Citation topics
- 1 Clinical & Life Sciences
- 1.6 Immunology
- 1.6.214 Checkpoint Inhibition
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology