Dendritic cells maturation and hyaluronan levels in mice injected with cell lines derived from a T cell lymphoma

CORDO RUSSO R; BLOIS SM; BLANCO G; ALVAREZ E; GARCÍA MG; HAJOS S

Berlin, Alemania

Congreso; 2 Congreso Europeo de Inmunología; 2009

Objectives: The existence of tolerance mechanisms allows tumour cells to grow in immunocompetent host. DCs, influenced by their microenvironment, may tolerize or stimulate the immune system against cancer. HA is a glycosaminoglycan increased in the extracellular matrix within tumours, related with tumour progression. HA fragments, but not native HA, induce DC maturation, generating an effective immune response. The aim of this work was to analyse the maturational state of DCs in the organs infiltrated by lymphoid tumours and its relationship with HA levels. For this purpose, we used murine lymphoma cell lines resistant to doxorubicin (LBR-D160), vincristine (LBR-V160), and a sensitive line (LBR-) with dissimilar invasive behaviour in vivo, being LBR-V160 the less aggressive one. Methods: BALB/c mice were injected with tumour cells or RPMI-1640, sacrificed at day 10 (non terminal state) and infiltrated liver, lung and lymph nodes were removed for the analysis of DCs presence (CD11c+ cells) and maturation (expression of CMH-II and CD80) by flow cytometry. Besides, serum HA was measured by ELISA. Data was analysed by one-way ANOVA and Dunnet´s post test. Results: Analysis of CD11c expression in liver showed that percentage of CD11c+ cells in mice inoculated with LBR- and LBR-D160 (5.3±0.7% and 5.9±0.9%) was significantly decreased compared with control mice (9.0±1.7%; P< 0.05), observing no differences in mice inoculated with LBR-V160 (11.7±2.6%). Besides, no changes in CD11c levels between the groups were observed in lymph nodes and lung. Analysis of CMH-II and CD80 expression in CD11c+ cells in liver showed a decrease in double positive cells in LBR- and LBR-D160 injected mice (11.3±4.4% and 17.6±5.2%) compared with control (37.1±10.1%; P< 0.05), finding no differences in LBR-V160 injected mice (35.8±14.9%). In lymph nodes, but not in lung, similar results were observed. Serum HA levels were increased in LBR- and LBR-D160 injected mice compared with LBR-V160 injected and control mice (P< 0.05). Conclusion: We conclude that mice injected with the cell lines with major invasive capacity (LBR- and LBR-D160) presented decreased DCs maturation in liver and lymph nodes as well as increased serum HA levels. We consider that this could be an obstacle in the induction of an effective antitumoral immune response.