Different antitumor immunity roles of cytokine activated T lymphocytes from naive murine splenocytes and from dendritic cells-based vaccine primed splenocytes: implications for adoptive immunotherapy.
OBJECTIVE
The aim of the study is to explore the antitumor capacity of effector cells generated from murine splenocytes with sequential addition of a cocktail of cytokines and the possible contribution of dendritic cells to the antitumor capacity of these effector cells.


RESULTS
Interferon-gamma, interleukin (IL)-1 beta, anti-CD3 mAb and IL-2 were used to activate murine splenocytes either from naive mice (termed cytokine activated T cells, CAT) or from DC based vaccine primed mice (termed specific effector T cells, SET). The antitumor roles of SET and CAT were analyzed in murine L615 T lymphocytic leukemia. Both CAT and SET were CD4(+)-predominant phenotypically and didn't show any significant cytotoxicity against a variety of syngeneic and allogeneic target cell lines using 51Cr release assay. When injected in vivo in combination with CY, CAT can cure a large proportion of leukemia mice. The cured mice couldn't establish specific antitumor immunity. However, in contrast to the roles of CAT, SET show far superior antitumor efficacy on a per cell basis compared with CAT. Moreover, the SET cured mice developed tumor specific long term memory immunity which was sufficient to reject a subsequent otherwise lethal tumor cells rechallenge and was transferable to naive immunocompetent mice.


CONCLUSIONS
Our data demonstrate that there remain fundamentally different antitumor functions of CAT and SET which might be useful in the immunotherapy strategy choices.
Zhang
Sheng
S
Oncology Center, Affiliated Hospital of Qingdao University Medical College, Qingdao, China. wozhangsheng@263.net
Wang
Qin
Q
Li
Wen-Feng
WF
Wang
Hong-Yi
HY
Zhang
Hong-Jun
HJ
Zhu
Jing-Juan
JJ
D000818:Animals; D019496:Cancer Vaccines / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D007156:Immunologic Memory; D016219:Immunotherapy, Adoptive; D007942:Leukemia, Experimental / Q000276:immunology* / Q000628:therapy; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D019496:Cancer Vaccines; D016207:Cytokines