The interaction between murine melanoma and the immune system reveals thatprolonged responses predispose for autoimmunity.

摘要

An assessment of antitumor immunity versus autoimmunity as provoked by thespecific depletion of Foxp3(+) Tregs is now possible with the development ofFoxp3-diphtheria toxin receptor-like transgenic mouse models. We have used thepoorly immunogenic B16F10 melanoma model to characterize a very heterogeneousantitumor effect of the immune response induced by Treg depletion. Depletion and neutralization studies demonstrated the importance of host T cells and interferonγ (IFNγ) in mediating the antitumor response developing in Treg-depleted mice.Such a response correlated with increased proliferation of granzyme B- andIFNγ-producing T cells in the tumor. Furthermore, enhanced antitumor immunitymodulated the expression of MHC Class I molecules by B16F10 melanoma cells inTreg-depleted mice. Since Foxp3(+) Treg depletion induced a significantlyheterogeneous antitumor response, for the first time we were able to assessantitumor immunity and autoimmunity across different groups of responding mice.Strikingly, the duration of the tumor-immune system interaction provoked inindividual Treg-depleted mice positively correlated with their propensity todevelop vitiligo. A rapid complete tumor rejection was not associated with thedevelopment of autoimmunity, however, a proportion of mice that suppressed, butdid not effectively clear, B16F10 melanoma did develop vitiligo.?The significant implication is that approaches that combine with Treg depletion to rapidly rejecttumors may also diminish autoimmune toxicities.?