Potent Tumor-Specific Protection Ignited by Adoptively Transferred

Administration of anti-CD25 mAb before an aggressive murine breast tumor inoculation provoked effective antitumor immunity. Compared with CD4 T cells purified from anti-CD25 mAb-pretreated mice that did not reject tumor, CD4 T cells purified from anti-CD25 mAb-pretreated mice that rejected tumor stimulated by dendritic cells (DCs) produced more IFN- and IL-2, and less IL-17 in vitro, and ignited protective antitumor immunity in vivo in an adoptive transfer model. Tumor Ag-loaded DCs activated naive CD8 T cells in the presence of these CD4 T cells in vitro. Tumor Ag and adoptively transferred CD4 T cells were both required for inducing a long-term tumor-specific IFN--producing cellular response and potent protective antitumor activity. Although adoptively transferred CD4 T cells ignited effective tumor-specific antitumor immunity in wild-type mice, they failed to do so in endogenous NK cell-depleted, Gr-1 cell-depleted, CD40/, CD11c DC-depleted, B cell/, CD8 T cell-depleted, or IFN-/ mice. Collectively, the data suggest that adoptively transferred CD4 T cells orchestrate both endogenous innate and adaptive immunity to generate effective tumor-specific long-term protective antitumor immunity. The data also demonstrate the pivotal role of endogenous DCs in the tumor-specific protection ignited by adoptively transferred CD4 T cells. Thus, these findings highlight the importance of adoptively transferred CD4 T cells, as well as host immune components, in generating effective tumor-specific long-term antitumor activity. The Journal of Immunology, 2008, 181: 4363–4370. T he CD4 T cells have emerged as an important arm of theimmune system in combating tumors (1–3). CD4 T cellscould mediate tumor rejection by killing tumor cells via TRAIL-, Fas ligand-, or granzyme-perforin-dependent pathways