Increased tumor growth due to attenuation of the immune response by tumor-induced systemic inflammation

JUAN BRUZZO; PAULA CHIARELLA; RAÚL A. RUGGIERO

Congreso; LVIII Reunion Anual de la Sociedad Argentina de Inmunologia; 2010

The link between cancer and inflammation has firmly been established on the basis that cancer tends to occur at sites of chronic inflammation and that local inflammatory processes can accelerate the growth of preexisting tumors in both experimental animals and human beings. On the other hand, the relationship between cancer and systemic inflammation has comparatively been less studied. The aim of this work was to evaluate the relationship between systemic inflammation (SI) and tumor growth. Tumor: immunogenic methylchonlanthrene-induce fibrosarcoma (MCC). We know that the MCC growth was accompanied by SI, and was more prominent when the tumor has exceeded 500 mm3. To determine if SI was followed by compensatory manifestations of systemic counter-inflammation (SCI), the anti-inflamamatory cytokines TGF-¥â and IL-10 were evaluated. In effect, there were an increase of both cytokines in serum of tumor-bearing mice at different times (p<0.05; p < 0.01, respectively). To determine the influence of SI /SCI on the tumor growth, indomethacin was inoculated intraperitoneal (i.p.), a decrease of the tumor growth was observed compared with the control (p<0.05). Furthermore, it was caused a transient SI with the i.p. inoculation of thioglycolate (TG), which accelerated the subcutaneous growth of MCC respected to control (p<0.01). To study if that exacerbation could be associated with deleterious effects produced by SI induced by TG on the immune system, it was evaluated if the use of TG affect the anti-tumor immune response, in mice bering MCC of less than 500 mm3, as well as  in immunized mice against MCC. In effect, the inoculation of TG at the time of the inoculation of the 2¨¬ tumor, as well as in immunized mice against MCC at the time of the tumor inoculation, showed a faster growth than its respectives controls (p<0.05; p<0.01, respectively). This results suggest that the exacerbation of MCC induced by SI, it would be at least partly, result of an attenuation of the anti-tumoral immune response.