CD40, BUT NOT CD40L OR CD80 INDUCED A BYSTANDER EFFECT ON TUMOR REJECTION OF A PARENTAL T-CELL LYMPHOMA

RUYBAL P; DI SCIULLO P; GRAVISACO MJ; WALDNER C; MONGINI C

Rio de Janeiro, Brazil.

Congreso; ImmunoRio 2007. The 13th International Congress of Immunology; 2007

We have previously demonstrated that CD40L, CD40, or CD80 expression on LBC tumor cells (LBC.40L, LBC.40 or LBC.80) significantly decreases tumorigenicity when compared to mock transfected (LBC.Mock) or wild-type LBC cells. This immunogenicity improvement is mediated by specific cytotoxic activity in LBC.CD40, cytotoxic T-cell and NK activation in LBC.CD80 and mostly NK activation in LBC.CD40L. The aim of this work was to analyze if tumor rejection achieved when inoculating cells transfected with tcr costimulatory molecules was dependent on the number of cells transfected vs wild type tumor cells in the inoculum. Syngeneic BALB/c mice were inoculated intraperitonealy with CD40, CD40L or CD80 LBC transfesfected cells mixed with wild type LBC cells in different proportions (0, 25, 50, 75 and 100%) with a final dose of 106 cells per mouse.  The percentage of survivors (%SV) was calculated and the time at which 50% of challenged mice had died (DT50) was recorded. The %SV and DT50 was drastically diminished when reducing the number of CD80 and CD40L LBC transfected tumor cells in the inoculum.  On the contrary even when only 25% of CD40.LBC cells mixed with LBC wild type can induce a strong immune response leading to the rejection of the tumor suggesting a bystander effect. The bystander effect exerted by the CD40 transfectants would be beneficial for eradicating a tumor mass by CD40 tumor transfected cells since only small amount of cells must be transfected to achieve the complete rejection by the immune system.