Induction of T-cell responses against cutaneous T-cell lymphomas ex vivo by autologous dendritic cells transfected with amplified tumor mRNA.
Sézary 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 Sézary 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 Sézary 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 Sézary 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.
Ni
Xiao
X
Department of Dermatology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA. Electronic address: xiaoni@mdanderson.org.
Richmond
Heather M
HM
Department of Dermatology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
Liao
Xingsheng M
XM
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.
Decker
William K
WK
Department of Stem Cell Transplantation and Cell Therapy, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
Shiue
Lisa H
LH
Department of Dermatology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
Shpall
Elizabeth J
EJ
Department of Stem Cell Transplantation and Cell Therapy, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
Duvic
Madeleine
M
Department of Dermatology, The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics*; D036122:Receptor, EphA4 / Q000378:metabolism; D012751:Sezary Syndrome / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D014162:Transfection / Q000379:methods*; D051879:Twist-Related Protein 1 / Q000378:metabolism
D017252:CD3 Complex; D053645:Interleukin-2 Receptor alpha Subunit; D012333:RNA, Messenger; D051879:Twist-Related Protein 1; D007371:Interferon-gamma; D036122:Receptor, EphA4; D053804:Granzymes