Antibody to Mac-1 or monocyte chemoattractant protein-1 inhibits monocyte recruitment and promotes tumor growth.
Human tumors are frequently infiltrated by numerous monocytes/macrophages, which can be found within the tumor mass (intratumoral) or surrounding the tumor (peritumoral). The functional role that these monocytes/macrophages play in tumor growth is controversial. To address this issue we inhibited intratumoral monocyte/macrophage recruitment with mAbs that either blocked integrin function or neutralized a tumor-produced chemotactic protein. Both treatments significantly increased tumor formation and accelerated tumor growth. Surprisingly, the same results were obtained when recruitment of peritumoral or intratumoral monocytes/macrophages was blocked. Our findings are contrary to one of the purported roles of monocytes/macrophages, particularly in the peritumoral area, since we found no evidence for monocyte/macrophage-supported tumor growth. These results provide direct evidence that intratumoral as well as peritumoral monocytes/macrophages act to limit tumor size in the early stages following tumor inoculation and provide a mechanism that accounts for monocyte/macrophage recruitment to human tumors.
Zhang
L
L
Department of Pathology and Laboratory Medicine, Boston University School of Medicine, MA 02118, USA.
Yoshimura
T
T
Graves
D T
DT
D000818:Animals; D018932:Chemokine CCL2 / Q000276:immunology*; D002634:Chemotaxis, Leukocyte; D006801:Humans; D016177:Macrophage-1 Antigen / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D009000:Monocytes / Q000276:immunology*; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000276:immunology
D018932:Chemokine CCL2; D016177:Macrophage-1 Antigen