REVERSION OF THE IMMUNOLOGICAL ECLIPSE IN TUMOR-BEARING MICE BY ANTIINFLAMMATORY TREATMENT.

CHIARELLA PAULLA; EVANGELINA LABORDE; VANZULLI, SILVIA; VERMEULEN MONICA; MARISA VULCANO; OSCAR D. BUSTUOABAD; RAÚL A. RUGGIERO

Congreso; ALAI; 2005

Although animals can be prophylactically immunized against the growth of tumor implants, all 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 used a strongly immunogenic murine fibrosarcoma (MC-C). We demonstrated that MC-C tumor-bearing mice can generate a T-cell mediated immune response against MC-C which disappears alter MC-C grows beyond 500 mm3. This immunological eclipse was associated with a high serum concentration of TNF-alfa and C-reactive protein (CRP) and a high number of both, circulating granulocytes and splenic Gr1+Mac1+ granulocytes (27±2 %) as compared with that present in normal mice (3±1 %) and in mice bearing small (< 500 mm3) tumors (5±1%), p<0.01. Number of splenic T reg CD4+CD25+ was not -increased. A dose of dexamethasone (50 µg/mouse) reduced significantly the number of both circulating granulocytes and splenic Gr1+Mac1+ granulocytes (10±2 %, p<0.02) as well as the serum concentration of TNF-alfa and CRP. These effects were associated with a significant improvement of the antitumor immune response similar to that found in mice bearing MC-C <500 mm3. The reversion of the immunological eclipse was not, itself, curative, but it may be the first step for eliminating the refractoriness of the tumor-bearing mice to any attempt of antitumor immunological therapy.