Regulating mammalian target of rapamycin to tune vaccination-induced CD8 + T cell responses for tumor immunity

Qingsheng Li, Rajesh Rao, Joseph Vazzana, Peter Goedegebuure, Kunle Odunsi, William Gillanders, Protul A. Shrikant

Research output: Contribution to journalArticle

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Abstract

Vaccine strategies aimed at generating CD8 + T cell memory responses are likely to show augmented efficacy against chronic challenges like tumor. The abundance in variety of memory CD8 + T cells behooves development of vaccine strategies that generate distinct memory responses and evaluate them for tumor efficacy. In this study, we demonstrate the ability of a variety of rapamycin treatment regimens to regulate virus vaccination-induced CD8 + T cell memory responses and tumor efficacy. Strikingly, a short course of high-dose, but not low-dose, rapamycin treatment transiently blocks viral vaccination-induced mammalian target of rapamycin activity in CD8 + T cells favoring persistence and Ag-recall responses over type 1 effector maturation; however, prolonged high-dose rapamycin administration abrogated memory responses. Furthermore, a short course of high-dose rapamycin treatment generated CD8 + T cell memory responses that were independent of IL-15 and IL-7 and were programmed early for sustenance and greater tumor efficacy. These results demonstrate the impact a regimen of rapamycin treatment has on vaccine-induced CD8 + T cell responses and indicates that judicious application of rapamycin can augment vaccine efficacy for chronic challenges.

Original languageEnglish (US)
Pages (from-to)3080-3087
Number of pages8
JournalJournal of Immunology
Volume188
Issue number7
DOIs
StatePublished - Apr 1 2012
Externally publishedYes

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Sirolimus
Immunity
Vaccination
T-Lymphocytes
Vaccines
Neoplasms
Interleukin-15
Interleukin-7
Aptitude
Therapeutics
Viruses

ASJC Scopus subject areas

  • Immunology

Cite this

Li, Q., Rao, R., Vazzana, J., Goedegebuure, P., Odunsi, K., Gillanders, W., & Shrikant, P. A. (2012). Regulating mammalian target of rapamycin to tune vaccination-induced CD8 + T cell responses for tumor immunity. Journal of Immunology, 188(7), 3080-3087. https://doi.org/10.4049/jimmunol.1103365

Regulating mammalian target of rapamycin to tune vaccination-induced CD8 + T cell responses for tumor immunity. / Li, Qingsheng; Rao, Rajesh; Vazzana, Joseph; Goedegebuure, Peter; Odunsi, Kunle; Gillanders, William; Shrikant, Protul A.

In: Journal of Immunology, Vol. 188, No. 7, 01.04.2012, p. 3080-3087.

Research output: Contribution to journalArticle

Li, Q, Rao, R, Vazzana, J, Goedegebuure, P, Odunsi, K, Gillanders, W & Shrikant, PA 2012, 'Regulating mammalian target of rapamycin to tune vaccination-induced CD8 + T cell responses for tumor immunity', Journal of Immunology, vol. 188, no. 7, pp. 3080-3087. https://doi.org/10.4049/jimmunol.1103365
Li, Qingsheng ; Rao, Rajesh ; Vazzana, Joseph ; Goedegebuure, Peter ; Odunsi, Kunle ; Gillanders, William ; Shrikant, Protul A. / Regulating mammalian target of rapamycin to tune vaccination-induced CD8 + T cell responses for tumor immunity. In: Journal of Immunology. 2012 ; Vol. 188, No. 7. pp. 3080-3087.
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