CONICET | Buscador de Institutos y Recursos Humanos

Tumor induced immune suppression is widespread in patients and experimental animals with malignant tumors and is likely to be a significant impediment to immunotherapy. Multiple mechanisms are thought to facilitate this suppression, being Myeloid Derived Suppressor Cells (MDSC) and T regulatory cells (Treg) major contributors. Our aim was to analyze the immunological status of BALB/C mice bearing LP07 (COX+) lung tumor (TBM) and treated with Indomethacin, an unspecific COX inhibitor. We determined 1) The content of MDSC and Treg in lymphoid organs (Spleen, Tumor draining lymph nodes-TDLN-) and tumor tissue at different times in tumor development, by FACS; 2) Arginase activity in lung, spleen, liver and tumor measured as ìg Urea/mg protein; 3) Specific DTH response with formalinized LP07 cells by the foot pad swelling assay. Results: the percentage of MDSC (CD11b+ Gr1+) augmented significantly in the spleen in advanced stages of tumor progression (33 days) (Normal: 2,57; TBM 10 days: 2,375; TBM 20 days: 5,6; TBM 33 days :8,33, p<0,05 vs Normal), while this effect was prevented with Indo treatment (4,6%).Tregs (CD25+FOXP3+CD4+) intratumor frequency peaked at 20 days of tumor growth. Moreover, Tregs frequency decreased significantly in TDLN with Indo treatment (p<0,05). Arginase activity increased in every tissue of TBM compared to normal mice. Specific DTH response decreased in late stages of tumor evolution, while Indo treatment reversed this inhibition (TBM:0,06 ± 0,045; Indo:0,14 ± 0,038). Conclusion: In our model the increase in MDSC along tumor growth correlates with the specific immunosuppression shown by DTH and with increased arginase activity. We suggest Indo treatment reversed immunosuppression by modulating COX activity, which is known to activate MDSC and differentiate Tregs.