IMMUNOBIOLOGY

The development of effective therapeutic vaccines to generate tumor-reactive cyto-toxic T lymphocytes (CTLs) continues to be a top research priority. However, in spite of some promising results, there are no clear examples of vaccines that eradi-cate established tumors. Most vaccines are ineffective because they generate low numbers of CTLs and because numerous immunosuppressive factors abound in tumor-bearing hosts. We designed a pep-tide vaccine that produces large numbers of tumor-reactive CTLs in a mouse model of melanoma. Surprisingly, CTL tumor recognition and antitumor effects de-creased in the presence of interferon (IFN), a cytokine that can provide thera-peutic benefit. Tumors exposed to IFN evade CTLs by inducing large amounts of noncognate major histocompatibility complex class I molecules, which limit T-cell activation and effector function. Our results demonstrate that peptide vac-cines can eradicate large, established tu-mors in circumstances under which the inhibitory activities of IFN are curtailed. (Blood. 2011;117(1):135-144