Blockade of PD-1/PD-L1 promotes adoptive T-Cell immunotherapy in a tolerogenic environment

Blake, Stephen J. P., Ching, Alan L. H., Kenna, Tony J., Galea, Ryan, Large, Justin, Yagita, Hideo and Steptoe, Raymond J. (2015) Blockade of PD-1/PD-L1 promotes adoptive T-Cell immunotherapy in a tolerogenic environment. PLoS One, 10 3: . doi:10.1371/journal.pone.0119483

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Author Blake, Stephen J. P.
Ching, Alan L. H.
Kenna, Tony J.
Galea, Ryan
Large, Justin
Yagita, Hideo
Steptoe, Raymond J.
Title Blockade of PD-1/PD-L1 promotes adoptive T-Cell immunotherapy in a tolerogenic environment
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2015-03-05
Year available 2015
Sub-type Article (original research)
DOI 10.1371/journal.pone.0119483
Open Access Status DOI
Volume 10
Issue 3
Total pages 21
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Language eng
Formatted abstract
Adoptive cellular immunotherapy using in vitro expanded CD8+ T cells shows promise for tumour immunotherapy but is limited by eventual loss of function of the transferred T cells through factors that likely include inactivation by tolerogenic dendritic cells (DC). The co-inhibitory receptor programmed death-1 (PD-1), in addition to controlling T-cell responsiveness at effector sites in malignancies and chronic viral diseases is an important modulator of dendritic cell-induced tolerance in naive T cell populations. The most potent therapeutic capacity amongst CD8+ T cells appears to lie within Tcm or Tcm-like cells but memory T cells express elevated levels of PD-1. Based on established trafficking patterns for Tcm it is likely Tcm-like cells interact with lymphoid-tissue DC that present tumour-derived antigens and may be inherently tolerogenic to develop therapeutic effector function. As little is understood of the effect of PD-1/PD-L1 blockade on Tcm-like CD8+ T cells, particularly in relation to inactivation by DC, we explored the effects of PD-1/PD-L1 blockade in a mouse model where resting DC tolerise effector and memory CD8+ T cells. Blockade of PD-1/PD-L1 promoted effector differentiation of adoptively-transferred Tcm-phenotype cells interacting with tolerising DC. In tumour-bearing mice with tolerising DC, effector activity was increased in both lymphoid tissues and the tumour-site and anti-tumour activity was promoted. Our findings suggest PD-1/PD-L1 blockade may be a useful adjunct for adoptive immunotherapy by promoting effector differentiation in the host of transferred Tcm-like cells.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
UQ Diamantina Institute Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 10 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 11 times in Scopus Article | Citations
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