Potential differentiation of tumor bearing mouse CD11b+Gr-1+ immature myeloid cells into both suppressor macrophages and immunostimulatory dendritic cells

Abstract

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.