To clarify mechanism by which long-term antitumor immunity induced by GM-CSF gene transduced tumor cells is generated in the absence of LTB4/BLT1 signaling.

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In this study, we successfully identified CD4+T cells as a pivotal determinant responsible for developing long-term antitumor effect during re-rejection of rechallenge of WEHI3B cells, a mouse monocytic leukemia cell line, after observation of marked rejection of in vivo s.c. administration of GM-CSF gene transduced WEHI3B (WGM) cells. In addition, ratios of various memory CD4+T cells including stem central memory CD4+T and CD8+ T cells in lymph nodes (LNs) collected at day 46 were increased in BLT1 mice inoculated with WGM cells. As a prospective mechanism, our immunological findings suggest that absence of LTB4/BLT1 signaling facilitates effective and sustained generation of potent tumor associated antigens (TAAs) specific memory CD4+T cells by promoting activation of mature DCs in LNs and migration of TAAs phagocytosed DCs into LNs, subsequently leading to augmented adaptive immunities (Th1 and Th2 cells) and repressing a wide range of regulatory CD4+ T cells known to hinder antitumor immunity.