Initiation of tumor immunosurveillance by mast cells

(Project leader: Tilo Biedermann, M.D.)

Abstract:

Immune reactions against melanomas occur spontaneously and this is called 'regression'. Thus, melanoma is considered a useful model disease for cancer immuno-therapy, but the consecutive steps that initiate spontaneous melanoma regression are not characterized.

Mast cells (MC) are considered potent immune modulators with both pro-inflammatory and regulatory function. We found the most prominent MC infiltrates in melanomas with spontaneous immune regression. Moreover, MC deficient Kit^W-sh and Kit^W/Kit^W-v mice showed accelerated melanoma growth compared to wildtype that could be reverted by MC reconstitution. In addition, activation of MC could compensate for dendritic cell (DC) activation indicating productive crosstalk between MC and DC underlying MC mediated induction of anti-tumor immunity.

Therefore, MC mediated tumor immunosurveillance will be analyzed including the characterization of consequences on T cell immunity in vitro and in vivo during melanoma growth using the appropriate knock-out models, MC knock-in experiments and mice with MC specific gene targeting (cre-flox system). This will allow us to characterize the role for MC in tumor immunosurveillance and results may define a new starting point for cancer immuno-therapy.

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