Potential differentiation of tumor bearing mouse CD11b+Gr-1+ immature myeloid cells into both suppressor macrophages and immunostimulatory dendritic cells.
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 (MPhi) 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-gamma 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.
Narita
Yoshinori
Y
Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
Wakita
Daiko
D
Ohkur
Takayuki
T
Chamoto
Kenji
K
Nishimura
Takashi
T
D000818:Animals; D039481:CD11b Antigen / Q000096:biosynthesis*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D007377:Interleukin-3 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000276:immunology*; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D013154:Spleen / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology
D039481:CD11b Antigen; C503133:Gr-1 protein, mouse; D007166:Immunosuppressive Agents; D007377:Interleukin-3; D019707:Receptors, Chemokine; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor