Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (Review)

  • Authors:
    • David W. Hoskin
    • Jamie S. Mader
    • Suzanne J. Furlong
    • David M. Conrad
    • Jonathan Blay
  • View Affiliations

  • Published online on: March 1, 2008     https://doi.org/10.3892/ijo.32.3.527
  • Pages: 527-535
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Abstract

The resistance of many human cancers to immune-based therapies, including adoptive immunotherapy and the administration of therapeutic cancer vaccines, has been attributed to tumor-associated immune suppression, due in part to immunosuppressive molecules located within the tumor microenvironment. Adenosine is a purine nucleoside found within the interstitial fluid of solid tumors at concentrations that are able to inhibit cell-mediated immune responses to tumor cells. It is well established that extracellular adenosine inhibits T lymphocyte activation and effector function, including T cell adhesion to tumor cells and cytotoxic activity, by signaling primarily through A2a and A3 adenosine receptors on the surface of T cells. Importantly, A2a adenosine receptor-deficient mice exhibit enhanced anti-tumor immune responses by CD8+ T cells, as well as a dramatic reduction in the growth of experimental tumors in comparison to wild-type controls. A2a adenosine receptor signaling has also been implicated in adenosine-mediated inhibition of cytokine production and cytotoxic activity by activated natural killer (NK) cells, although the process of NK cell granule exocytosis is apparently suppressed via a distinct and as yet uncharacterized adenosine receptor. In this report, we review the evidence that adenosine is a potent inhibitor of cellular immune responses and may therefore be a major barrier to the successful immunotherapy of human carcinomas. The signaling pathways through which adenosine exerts its inhibitory effects on cell-mediated immune responses are also discussed. The accumulated evidence suggests that the effectiveness of immune-based therapies for solid tumors may be enhanced by selective antagonism of the adenosine receptor subtypes through which adenosine inhibits the anti-tumor activity of T lymphocytes and NK cells.

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March 2008
Volume 32 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Hoskin DW, Mader JS, Furlong SJ, Conrad DM and Blay J: Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (Review). Int J Oncol 32: 527-535, 2008.
APA
Hoskin, D.W., Mader, J.S., Furlong, S.J., Conrad, D.M., & Blay, J. (2008). Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (Review). International Journal of Oncology, 32, 527-535. https://doi.org/10.3892/ijo.32.3.527
MLA
Hoskin, D. W., Mader, J. S., Furlong, S. J., Conrad, D. M., Blay, J."Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (Review)". International Journal of Oncology 32.3 (2008): 527-535.
Chicago
Hoskin, D. W., Mader, J. S., Furlong, S. J., Conrad, D. M., Blay, J."Inhibition of T cell and natural killer cell function by adenosine and its contribution to immune evasion by tumor cells (Review)". International Journal of Oncology 32, no. 3 (2008): 527-535. https://doi.org/10.3892/ijo.32.3.527