Monocyte chemoattractant protein inhibits the generation of tumor-reactive T cells.
The adoptive transfer of tumor-sensitized T cells can eradicate disseminated malignancy in murine animal models. T cells must be sensitized to tumor antigens in vivo to acquire antitumor reactivity. T-cell sensitization has been demonstrated to be dependent on host antigen-presenting cells. Tumor-associated macrophages are a heterogeneous population of cells that may have both inhibitory and stimulatory influences on the sensitization of naive T cells. Here we demonstrate that a weakly immunogenic tumor, the MCA 205 sarcoma, produces substantial amounts of murine monocyte chemoattractant protein 1 (MCP-1). Neutralization of MCP-1 during in vivo T-cell sensitization resulted in T cells that possessed enhanced therapeutic activity against established pulmonary metastases. These T cells sensitized during MCP-1 depletion also exhibited enhanced production of IFN-gamma upon recognition of tumor targets. These results demonstrate that MCP-1 can have a potent inhibitory influence on the development of tumor-reactive T cells.
Peng
L
L
The Center for Surgery Research, The Cleveland Clinic Foundation, Ohio 44195, USA.
Shu
S
S
Krauss
J C
JC
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002273:Carcinogens; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D005260:Female; D016219:Immunotherapy, Adoptive; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000502:physiology*; D008264:Macrophages / Q000276:immunology / Q000502:physiology; D008748:Methylcholanthrene; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D013047:Specific Pathogen-Free Organisms
D000906:Antibodies; D002273:Carcinogens; D018932:Chemokine CCL2; D009363:Neoplasm Proteins; D008748:Methylcholanthrene