Dendritic cells pulsed with apoptotic squamous cell carcinoma have anti-tumor effects when combined with interleukin-2.
OBJECTIVE
Dendritic cells, the most potent of the antigen-presenting cells, have been widely studied as a promising tool for antitumor immunotherapies. However, little has been determined about the efficacy of dendritic cell-based therapy for the treatment of squamous cell carcinoma (SCC) because there are no known SCC-specific antigens. Recent reports indicate that dendritic cells can acquire antigens in the form of apoptotic cells and induce cytotoxic T-lymphocyte responses. The aim of this study was to test the feasibility of adoptive dendritic cell immunotherapy against SCC by using apoptotic tumor cells as a source of tumor antigens.


METHODS
A poorly immunogenic SCC line KLN 205 was used to make subcutaneous tumors on the flank of DBA2/J syngeneic mice. Bone marrow-derived dendritic cells were pulsed with ultraviolet B-irradiated (apoptotic) KLN 205 cells in vitro and transferred to the opposite flank subcutaneously. Some of the animals received simultaneous intraperitoneal injections of low-dose interleukin-2.


RESULTS
When combined with interleukin-2, adoptive transfers of dendritic cells that were pulsed with apoptotic SCC significantly suppressed the tumor growth (P <.001) without notable side effects. Splenic T cells of treated mice produced greater amounts of interferon-gamma when restimulated with the relevant tumor (P <.001) as compared with control groups, indicative of an effective T-cell-mediated systemic immune response.


CONCLUSIONS
Adoptive transfer of dendritic cells pulsed with apoptotic tumor cells as a source of tumor antigens, can elicit effective antitumor responses in the poorly immunogenic SCC model when combined with interleukin-2.
Son
Y I
YI
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, U.S.A. yison@smc.samsung.co.kr
Mailliard
R B
RB
Watkins
S C
SC
Lotze
M T
MT
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000627:therapeutic use*; D051379:Mice; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000276:immunology
D007376:Interleukin-2