[Reversion of the immunological eclipse and therapeutic vaccination against cancer in an experimental model].
Although animals can be prophylactically immunized against the growth of tumor implants, most of the attempts to use immunotherapy to cause the regression of animal and human tumors once they become established have been unsuccessful. To understand the nature of this refractoriness we have studied a methylcholanthrene-induced and strongly immunogenic murine fibrosarcoma. In our model, the onset of this refractoriness was associated with the beginning of an immunosuppressive state known as "immunological eclipse" characterized by a loss of the antitumor immune response when tumor grows beyond a critical size. This immunological eclipse was accompanied by the emergence of a systemic inflammatory condition. Treatment of tumor-bearing mice with a single dose of a synthetic corticosteroid, dexamethasone (DX), reduced significantly all parameters of systemic inflammation and simultaneously reversed the immunological eclipse. The reversion of the eclipse upon DX treatment was not curative itself, but allowed an immunological therapy based in dendritic cells pulsed with tumor antigens, which was itself absolutely ineffective, to exert a significant inhibitory effect against an established growing tumor. The two-step schedule using an anti-inflammatory treatment to reverse the immunological eclipse plus a dendritic cell-based vaccination strategy aimed to stimulate the antitumor immune response, could serve eventually as a model of immunotherapy against animal and human tumors.
Chiarella
Paula
P
División Medicina Experimental, Instituto de Investigaciones Hematológicas, Academia Nacional de Medicina, Buenos Aires, Argentina. paulachiarella@argentina.com
Vulcano
Marisa
M
Laborde
Evangelina
E
Vermeulen
Monica
M
Bruzzo
Juan
J
Rearte
Barbara
B
Bustuoabad
Oscar D
OD
Ruggiero
Raul A
RA
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002273:Carcinogens; D003713:Dendritic Cells / Q000276:immunology*; D003907:Dexamethasone / Q000276:immunology / Q000627:therapeutic use; D018572:Disease-Free Survival; D005354:Fibrosarcoma / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007249:Inflammation / Q000188:drug therapy; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D012513:Sarcoma, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology
D000893:Anti-Inflammatory Agents; D019496:Cancer Vaccines; D002273:Carcinogens; D008748:Methylcholanthrene; D003907:Dexamethasone