To compare different groups, we used either Fishers exact test or the KruskalWallis test followed by Dunns test. presence of PNLIPRP2 autoantibodies. Analyses of MIAknown to be preferentially expressed in malignant cellssurprisingly revealed an inverse correlation between intratumoral gene PP242 (Torkinib) expression and the emergence of autoantibodies. MIAhighpatients were autoantibody-negative and had shorter median survival when compared with autoantibody-positive MIAlowpatients (12 vs. 34 months). The observed pTAA spectrum comprised molecules associated with acinar, stromal and malignant structures, thus presenting novel targets for tumor cell-specific therapies as well as for approaches based on the bystander effects. Applying the concept of cancer immunoediting to interpret relationships between gene expression, antitumor immune responses, and clinical outcome might better discriminate between past and ongoing immune responses, consequently enabling prognostic stratification of patients and individual adjustment of immunotherapy. == Electronic supplementary material == The online version of this article (doi:10.1007/s00262-010-0870-9) contains supplementary material, which is available to authorized users. Keywords:Pancreatic cancer, Immunoediting, SEREX, PNLIPRP2, MIA, Antibody == Introduction == Pancreatic cancer remains one of the most deadly malignancies despite sustained immunocompetence and tumor-specific immune responses detected in patients at various stages of cancer progression (http://www-dep.iarc.fr/) [112]. Induction of immune responses to known tumor-associated antigens (TAAs) has also not yielded a clear clinical benefit in patients with pancreatic cancer [1318]. Poor clinical response despite antitumor immunity is one of the most intriguing paradoxes of cancer [1921]. Decades of experimental work have laid the groundwork for the concept of cancer immunoediting, which emphasizes dual role of immunity in not only preventing, but also shaping neoplastic disease. A broadened form of the immunosurveillance theory, immunoediting views tumor progression as a dynamic process in which the immune system sculpts the non-edited antigenic repertoire of a tumor toward emergence of edited antigen-loss variants over an EliminationEquilibriumEscape continuum [2224]. In pancreatic cancer, spontaneous humoral responses (assumed to reflect antigen-specific T-cell responses) correlate with both better and worse outcomes [2529]. PP242 (Torkinib) The concept of immunoediting could provide a logical explanation for the lack of clinical benefit of immune PP242 (Torkinib) responses against tumors PP242 (Torkinib) in which the corresponding antigen is already lost: responses measurable at later stages of the disease reflect past events which are potentially prognostic, but no longer have therapeutic relevance. The presence of antibodies that reflect an immune response which eliminated immunogenic tumor cells with extremely pro-malignant functionsthus allowing expansion of less-aggressive variantswill have a positive prognostic value. Conversely, detection of antibodies reflecting immune responses eliminating less malignant tumor variantsthus favoring expansion of super-aggressive non-immunogenic specieswill have negative prognostic value. However, with immune effectors persisting after a target is eliminated, peptide-based vaccination approaches would fail while inducing recall responses without clinical impact. Thus, individual immunogenicity of TAA might enable immunoediting, which in turn might alter the TAA profile in a way which will greatly affect outcome. An immunogenic repertoire of a disease can be determined by different proteomic methods, the most comprehensive being the SEREX (Serological analysis of Recombinant cDNA Expression libraries) [3033]. To date, the SEREX method for the identification of pancreatic TAA (pTAA) has been restricted to libraries constructed from a cell line or from testis tissue, but not from pancreatic cancer specimens [3436]. The identity of the detected immunogenic TAA (1) differed among these heterologous approaches, (2) did not match the few findings deposited in the Cancer Immunome Database (http://ludwig-sun5.unil.ch/CancerImmunomeDB) which were obtained by other proteomic methods or reported by the SEREX study conducted in a syngeneic mouse model [3742], and (3) was not interpreted in relation to antigen expression PP242 (Torkinib) and clinical outcome. In the current study, we sought to comprehend the spectrum of pTAA and to determine whether immunogenicity of pTAA is relevant for disease outcome. We applied an autologous SEREX-based screening to establish the profile of immunogenic pTAA in a long-term survivor, reasoning that this patient was more likely to have a protracted equilibrium phase because of tumor displaying immunogens with potentially positive prognostic value. The association of immunogenicity with humoral responses capable of editing the antigenic repertoire of malignant cells in a prognostically relevant way was further explored by analyzing the relationship between pTAA expression, emergence of autoantibodies, and survival time in patients with pancreatic cancer. == Materials and methods == == Sample collection == The study was approved by the Medical Ethics Committee of the University of Heidelberg (case numbers 159/2002 and 301/2001). Upon written informed consent from the patients, tissue and sera specimens were collected in accordance with governmental and international regulations. The primary sera screening cohort included 20 healthy donors (4 females, 16 Kinesin1 antibody males; median age 60 years) and 34 pancreatic.