PMID- 21107834
OWN - NLM
STAT- MEDLINE
DCOM- 20110406
LR  - 20211203
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 60
IP  - 3
DP  - 2011 Mar
TI  - Rapamycin increases the yield and effector function of human gammadelta T cells 
      stimulated in vitro.
PG  - 361-70
LID - 10.1007/s00262-010-0945-7 [doi]
AB  - Clinical strategies to exploit Vgamma2Vdelta2 T cell responses for immunotherapy are 
      confronted with short-term increases in cell levels or activity and the 
      development of anergy that reduces the response to therapy with succeeding 
      treatments. We are exploring strategies to increase the yield and durability of 
      elicited Vgamma2Vdelta2 T cell responses. One approach focuses on the mammalian target of 
      rapamycin (mTOR), which is important for regulating T cell metabolism and 
      function. In Vgamma2Vdelta2 T cells, mTOR phosphorylates the S6K1 and eIF4EBP1 signaling 
      intermediates after antigen stimulation. Rapamycin inhibited these 
      phosphorylation events without impacting Akt or Erk activation, even though 
      specific inhibition of Akt or Erk in turn reduced the activation of mTOR. The 
      effects of rapamycin on the T cell receptor signaling pathway lead to increased 
      proliferation of treated and antigen-exposed Vgamma2Vdelta2 cells. Rapamycin altered the 
      phenotype of antigen-specific Vgamma2Vdelta2 cells by inducing a population shift from 
      CD62L + CD69- to CD62L-CD69+, higher expression of CD25 or Bcl-2, lower levels of 
      CCR5 and increased resistance to Fas-mediated cellular apoptosis. These changes 
      were consistent with rapamycin promoting cell activation while decreasing the 
      susceptibility to cell death that might occur by CCR5 or Fas signaling. Rapamycin 
      treatment during antigen-stimulation of Vgamma2Vdelta2 T cells may be a strategy for 
      overcoming current obstacles in tumor immunotherapy.
FAU - Li, Haishan
AU  - Li H
AD  - Institute of Human Virology, University of Maryland School of Medicine, 725 W. 
      Lombard St. Rm. N546, Baltimore, MD 21201, USA.
FAU - Pauza, C David
AU  - Pauza CD
LA  - eng
GR  - R01 CA142458/CA/NCI NIH HHS/United States
GR  - R01 CA142458-02/CA/NCI NIH HHS/United States
GR  - CA142458/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20101125
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (IL2RA protein, human)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Receptors, Antigen, T-Cell, gamma-delta)
RN  - 0 (Receptors, CCR5)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Antibiotics, Antineoplastic/*pharmacology
MH  - Antigen-Presenting Cells/drug effects
MH  - Apoptosis/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Flow Cytometry
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - In Vitro Techniques
MH  - Interleukin-2 Receptor alpha Subunit/metabolism
MH  - Lymphocyte Activation/drug effects
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Receptors, Antigen, T-Cell, gamma-delta/metabolism
MH  - Receptors, CCR5/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*pharmacology
MH  - T-Lymphocytes/*drug effects/metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC3077899
MID - NIHMS265181
COIS- The authors have no financial conflicts of interest related to this study.
EDAT- 2010/11/26 06:00
MHDA- 2011/04/07 06:00
PMCR- 2010/11/25
CRDT- 2010/11/26 06:00
PHST- 2010/07/16 00:00 [received]
PHST- 2010/11/05 00:00 [accepted]
PHST- 2010/11/26 06:00 [entrez]
PHST- 2010/11/26 06:00 [pubmed]
PHST- 2011/04/07 06:00 [medline]
PHST- 2010/11/25 00:00 [pmc-release]
AID - 945 [pii]
AID - 10.1007/s00262-010-0945-7 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2011 Mar;60(3):361-70. doi: 10.1007/s00262-010-0945-7. 
      Epub 2010 Nov 25.