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.

Abstract

Aim: 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.

Methods and 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.

Conclusion: Our data demonstrate that there remain fundamentally different antitumor functions of CAT and SET which might be useful in the immunotherapy strategy choices.