Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 39, Issue 5, Pages 1252-1259Publisher
WILEY-BLACKWELL
DOI: 10.1002/eji.200839152
Keywords
Anti-tumor immunity; Autoimmunity; CD4(+) T cells; Cytokines; Vaccination
Categories
Funding
- Canadian Institutes of Health Research [MOP-67066]
- Ontario Cancer Research Network
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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.
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