Structurespecic DNA endonuclease MusEme generates DNA damage caused by Chk inactivation. Rozenblum E, Schutte M, Goggins M, Hahn SA, Panzer S, Zahurak M, et al.Cancer Res. Published OnlineFirst June; DOI. Click on Request Permissions which will take you to the Copyright Clearance Centers Downloaded from clincancerres.aacrjournals.org on April. American Association for Cancer Research. By using a reverseimmunology approach, we show here that the inhibitor of apoptosis protein, survivin, is immunogenic in colorectal cancer patients.In particular, we found that survivin elicited CD T cellmediated responses in peripheral blood or in tumorassociated lymphocytes from patients at different disease stage.These findings indicate that survivin could be considered a valuable tumorassociated antigen for immunebased clinical approaches in colorectal cancer.INTRODUCTION CRC is one of the most common and dreadful malignancies, for which surgery remains the main therapeutic option, although the success of the treatment depends on the disease stage.Unfortunately, the majority of patients present at diagnosis with already advanced local disease with microscopic spread to local lymph nodes; for these patients the life expectancy does not exceed months. Although adjuvant systemic chemotherapy or chemoradiation has shown a limited but significant survival advantage, novel and more effective therapies are needed.CRC has been considered poorly immunogenic and, therefore, refractory to immunebased interventions.These findings support the conclusion that CRC could be immunogenic in vivo and imply that strategies aimed at potentiating immuneresponses may lead to a clinical benefit when administered in an adjuvant setting. The costs of publication of this article were defrayed in part by the payment of page charges.Although present also in normal colonic mucosa, these proteins are overexpressed in CRC, and immunotherapy approaches exploiting these antigens have led to the in vivo expansion of a systemic antigenspecific immunity, although only occasionally associated with objective clinical responses. Ideal targets for immunotherapy are gene products silenced in normal tissues, overexpressed in cancer cells, and directly involved in tumor survival and progression.Boosting the immune response against this type of proteins can be a strategy that, avoiding or at least limiting the in vivo generation of antigenloss variants, could be more efficient in the control of in vivo tumor growth and in affecting the disease prognosis.First, it is practically undetectable in normal differentiated tissues but overexpressed in most human cancers. Second, survivin is endowed with dual functions and, in addition to suppress apoptosis, it is also involved in regulating cell division. In proliferating cells, survivin reaches maximal levels in GM phase and becomes downregulated in G phase.Because of its cellcycleregulated expression and tumor specificity, survivin is thought to directly confer a selective growth advantage to tumor cells, allowing their progression through mitosis and leading to resistance to proapoptotic drugs. In agreement with these functions, survivin overexpression correlates with tumor progression and appears to be a bad prognostic factor for a variety of solid tumors including CRC. Therefore, survivin may be operationally considered a potential TAA, provided that such Galanthamine protein encompasses peptide epitopes recognized by T cells of cancer patients.In the present study, we aimed at assessing such a hypothesis in CRC patients.