PMID- 18480841
OWN - NLM
STAT- MEDLINE
DCOM- 20081030
LR  - 20230202
IS  - 1523-1747 (Electronic)
IS  - 0022-202X (Linking)
VI  - 128
IP  - 11
DP  - 2008 Nov
TI  - Induction of T-cell responses against cutaneous T-cell lymphomas ex vivo by 
      autologous dendritic cells transfected with amplified tumor mRNA.
PG  - 2631-2639
LID - S0022-202X(15)33662-9 [pii]
LID - 10.1038/jid.2008.125 [doi]
AB  - Sezary syndrome (SzS), the leukemic variant of cutaneous T-cell lymphomas, is 
      incurable. Dendritic cells (DCs) transfected with tumor mRNA can stimulate 
      antitumor immunity in certain cancer patients. In this study, we determined 
      whether mRNAs from Sezary cells could be used for loading DCs and stimulating 
      antitumor immunity. Autologous DCs were generated from monocytes of the 
      peripheral blood from 10 patients with SzS. Total RNA was extracted from Sezary 
      cells and amplified by T7 in vitro transcription. The induction of antitumor 
      IFN-gamma and granzyme B (GrB)-producing cytotoxic T lymphocytes (CTL) by 
      RNA-transfected DCs was determined by ELISPOT assays. We found that IFN-gamma was 
      required for IL-12p70 production by monocyte-derived DCs from SzS. The oncogenic 
      transcription factor Twist and the tyrosine kinase receptor EphA4 were expressed 
      in total RNA from Sezary cells and the paired amplified mRNAs. RNA-transfected 
      DCs induced antitumor IFN-gamma-producing CTLs in 7 of 10 subjects and 
      GrB-producing CTLs in 6 of 9 subjects. Both CD3+CD8+ T cells and CD4+CD25+ T 
      cells were expanded without induction of regulatory T cells. These data support 
      the concept of using tumor mRNA for a vaccine strategy that requires small 
      amounts of tumor cells without need for specific antigens in patients with SzS.
FAU - Ni, Xiao
AU  - Ni X
AD  - Department of Dermatology, The University of Texas, MD Anderson Cancer Center, 
      Houston, Texas, USA. Electronic address: xiaoni@mdanderson.org.
FAU - Richmond, Heather M
AU  - Richmond HM
AD  - Department of Dermatology, The University of Texas, MD Anderson Cancer Center, 
      Houston, Texas, USA.
FAU - Liao, Xingsheng M
AU  - Liao XM
AD  - Department of Dermatology, The University of Texas, MD Anderson Cancer Center, 
      Houston, Texas, USA; Division of Clinical Research, Fred Hutchinson Cancer 
      Research Center, Seattle, Washington, USA.
FAU - Decker, William K
AU  - Decker WK
AD  - Department of Stem Cell Transplantation and Cell Therapy, The University of 
      Texas, MD Anderson Cancer Center, Houston, Texas, USA.
FAU - Shiue, Lisa H
AU  - Shiue LH
AD  - Department of Dermatology, The University of Texas, MD Anderson Cancer Center, 
      Houston, Texas, USA.
FAU - Shpall, Elizabeth J
AU  - Shpall EJ
AD  - Department of Stem Cell Transplantation and Cell Therapy, The University of 
      Texas, MD Anderson Cancer Center, Houston, Texas, USA.
FAU - Duvic, Madeleine
AU  - Duvic M
AD  - Department of Dermatology, The University of Texas, MD Anderson Cancer Center, 
      Houston, Texas, USA.
LA  - eng
GR  - K24 CA86815/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20080515
PL  - United States
TA  - J Invest Dermatol
JT  - The Journal of investigative dermatology
JID - 0426720
RN  - 0 (CD3 Complex)
RN  - 0 (Interleukin-2 Receptor alpha Subunit)
RN  - 0 (RNA, Messenger)
RN  - 0 (Twist-Related Protein 1)
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 2.7.10.1 (Receptor, EphA4)
RN  - EC 3.4.21.- (Granzymes)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - CD3 Complex/metabolism
MH  - CD4-Positive T-Lymphocytes/metabolism/pathology
MH  - CD8-Positive T-Lymphocytes/metabolism/pathology
MH  - Female
MH  - Granzymes/metabolism
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Interleukin-2 Receptor alpha Subunit/metabolism
MH  - Langerhans Cells/*immunology/pathology
MH  - Leukocytes, Mononuclear/metabolism/pathology
MH  - Male
MH  - Middle Aged
MH  - RNA, Messenger/*genetics
MH  - Receptor, EphA4/metabolism
MH  - Sezary Syndrome/genetics/*immunology/pathology
MH  - Skin Neoplasms/genetics/*immunology/pathology
MH  - T-Lymphocytes, Cytotoxic/*immunology/pathology
MH  - Transfection/*methods
MH  - Twist-Related Protein 1/metabolism
EDAT- 2008/05/16 09:00
MHDA- 2008/10/31 09:00
CRDT- 2008/05/16 09:00
PHST- 2008/05/16 09:00 [pubmed]
PHST- 2008/10/31 09:00 [medline]
PHST- 2008/05/16 09:00 [entrez]
AID - S0022-202X(15)33662-9 [pii]
AID - 10.1038/jid.2008.125 [doi]
PST - ppublish
SO  - J Invest Dermatol. 2008 Nov;128(11):2631-2639. doi: 10.1038/jid.2008.125. Epub 
      2008 May 15.