TY - JOUR T1 - Induction of Wnt-Inducible Signaling Protein-1 Correlates with Invasive Breast Cancer Oncogenesis and Reduced Type 1 Cell-Mediated Cytotoxic Immunity: A Retrospective Study A1 - Klinke II, David J. Y1 - 2014/01/09 N2 - Author Summary Effective anti-tumor immunity is proportional to the number and to the cytotoxic activity of immune cells that enter the tumor microenvironment. Recent advances in cancer immunotherapy stem from increasing the number of tumor-infiltrating immune cells by inhibiting immune checkpoints or adoptive T cell therapy. Here, we used computational methods to identify potential mechanisms present within the tumor microenvironment that limit the efficacy of anti-tumor immunity. Specifically, we found that oncogenic transformation is associated with the induction of tumor-derived biochemical cues, namely Wnt-inducible signaling protein-1, that locally suppress anti-tumor immunity. Moreover, we used model-based inference to demonstrate that a gene signature consistent with effective type 1 cell-mediated cytotoxic immunity is a predictor of overall survival independent of molecular pathology. Interestingly, patients with triple negative breast cancer were more enriched in the cohort associated with type 1 cell-mediated immunity. As this immune gene signature is not present in current genetically engineered mouse models of breast cancer, the results help identify design constraints for engineering better pre-clinical models of breast cancer. Demonstrating efficacy in pre-clinical animal models is a pre-requisite for bringing improved cancer immunotherapies into the clinic. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 10 IS - 1 UR - https://doi.org/10.1371/journal.pcbi.1003409 SP - e1003409 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1003409 ER -