Evaluation of immunosuppressive tumor-escape mechanisms in tumor-bearing hosts is of great importance for the development of an efficient tumor immunotherapy. We document here the functional characteristics of CD11b+Gr-1+ immature myeloid cells (ImC), which increase abnormally in tumor-bearing mice. Although it has been reported that ImC exhibit a strong immunosuppressive activity against T cell responses, we demonstrate that ImC derived from tumor-bearing mouse spleens (TB-SPL) did not exhibit a strong inhibitory activity against CTL generation in MLR. However, ImC isolated from TB-SPL and induced to differentiate into CD11b+Gr-1+F4/80+ suppressor macrophages (MΦ) under the influence of tumor-derived factors were immunosuppressive. Furthermore, we also demonstrate that ImC isolated from TB-SPL had a capability of differentiating into immunostimulatory dendritic cells (DC1) supportive of the generation of IFN-γ producing CTL if the ImC were cultured with Th1 cytokines plus GM-CSF and IL-3. Thus, our findings indicate that tumor bearing mouse-derived CD11b+Gr-1+ ImC are not committed to development into immunosuppressor cells but have dual differentiation ability into both immunosuppressive myeloid cells and immunostimulatory DC1.

Antigen presenting cells (APC) such as DC and MΦ are critical immunoregulatory cell populations involved in host immune responses against tumors and infectious diseases. In particular, DC are the most potent APC for triggering CD4+ T cell and CD8+ T cell-mediated immune responses through MHCs, co-stimulatory molecules, and cytokines (20, 23, 27). Conversely, the dysfunction of DC results in the attenuation of host immune defense mechanisms against tumors and pathogens because of insufficient T cell stimulation.