title: CD4+ T-cell-mediated anti-tumor immunity can be uncoupled from autoimmunity via the STAT4/STAT6 signaling axis.
abstract: Previous reports have suggested that autoimmune sequelae may be an unavoidable consequence of successful immunization against tumor-associated antigens, which are typically non-mutated self-antigens. Using a melanoma model, we demonstrated that CD4(+) T-cell-mediated anti-tumor immunity and autoimmunity could be separated by modulating the STAT4/STAT6 signaling axis. Our results have revealed an unexpected dichotomy in the effector phase following cancer vaccination where anti-tumor immunity is mediated via a STAT6 and IL-4-dependent pathway, whereas autoimmune pathology is mediated via STAT4 through a mechanism that relies partially on IFN-gamma. Our results offer a possibility to elicit specific anti-tumor responses without triggering unwanted tissue autoimmune diseases.
authors.affiliation: Department of Pathology and Molecular Medicine, McMaster University, Ontario, Canada.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Dannie
authors.initials: D
authors.lastname: Bernard
authors.forename: Waliul I
authors.initials: WI
authors.lastname: Khan
authors.forename: Mark H
authors.initials: MH
authors.lastname: Kaplan
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Bramson
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Wan