Marra et al. BMC Cancer 2010, 10:129 http://www.biomedcentral.com/1471-2407/10/129 interaction between PSCA and IFNa/b receptor. PSCA is a GPI-anchored protein located in lipid raft. IFNa/b receptor can be brought into this subcellular compart- ment upon interaction with its ligands [29]. Thus, PSCA may counteract intracellular signaling exerted by the IFNa/b receptor playing a role as a defense protein. This biological role is reminiscent of the interfering role played by PSCA homolog, CD59, in the complement system [30]. Activation of the complement system is tightly regulated and among the various regulators CD59 has been identified as the single membrane regu- lator of the terminal membrane attack complex. More- over CD59 has been characterized as a negative regulator of the T-cell response in mice. Although we limited our qPCR confirmation only to IFNa/b pathway, a statistical significant up regulation was observed also for other immune pathways such as of MHC-1 pathway. Given the pleiotropic effects of IFNa/b pathway it is likely that some pathways, including MHC-1 presenta- tion, may be affected downstream. A more in depth ana- lysis would be required to answer this question. Finally we cannot exclude that the correlations observed only in tumors and not in cell culture are driven by unde- fined factors that are not captured in the expression profile and deserve further investigation. Conclusions The current findings suggest a role of PSCA in counter- acting the natural immune response against cancer. This information could help in design more effective experi- ments in preclinical models not only with monoclonal antibodies but also with approaches based on cancer vaccine [31-35]. It would be of interest to correlate anti- tumor efficacy of PSCA-targeting therapies as a function of the natural immune response. Acknowledgements The authors thank Aya Jakobovits and Jean Gudas for anti PSCA antibody, 4.117. The authors also thank Brendan Leeson and Ernest Coffey from Gene Expression Laboratories - Rosetta and LAR personnel for technical support. This work was partially supported by Progetto Integrato Oncologia, Ministero della Salute e Associazione Italiana per la Ricerca sul Cancro (AIRC). Author details 1Istituto di Ricerche Biologia Molecolare P. Angeletti (IRBM), Via Pontina Km 30,600 00040 Pomezia (Rome) Italy. 2Okairos, Via dei Castelli Romani 22, 00040 Pomezia (Rome) Italy. 3Istituto Superiore di Sanità (ISS), Viale Regina Elena 299, 00161 (Rome) Italy. 4Breakthrough Breast Cancer Research Unit, King’s College London, UK. Authors’ contributions EM generated cell lines expressing shRNA, analyzed PSCA expression by FACS analysis and performed experiments in vivo. PU performed microarray analysis and pathway analysis- VV generated cell lines expressing shRNA and performed IHC on tumor samples. VS performed qPCR analysis. ED contributed to the discussion of the data. EDR contributed in the discussion of the bioinformatics data and helped in drafting bioinformatics result section. AL performed the initial microarray analysis and contributed to data analysis. NLM, AN and GC contributed to the drafting and general discussion Page 8 of 9 of the paper. FP conceived the study, analyzed the data and wrote the manuscript. All authors read and approved the final manuscript. Competing interests The authors declare that they have no competing interests. Received: 25 November 2009 Accepted: 7 April 2010 Published: 7 April 2010 References 1. Reiter RE, Gu Z, Watabe T, Thomas G, Szigeti K, Davis E, Wahl M, Nisitani S, Yamashiro J, Le Beau MM, et al: Prostate stem cell antigen: a cell surface marker overexpressed in prostate cancer. Proc Natl Acad Sci USA 1998, 95:1735-1740. 2. Rodriguez JA, Li M, Yao Q, Chen C, Fisher WE: Gene overexpression in pancreatic adenocarcinoma: diagnostic and therapeutic implications. World J Surg 2005, 29:297-305. 3. 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