Regulatory Networks of Immune Evasion in Metastatic Prostate Cancer
Technical Report,01 Jun 2018,31 May 2019
Regents of the University of Michigan Ann Arbor United States
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Metastatic castration resistant PCa mCRPC is a very heterogeneous disease at molecular level, which is manifested by the highly variable rates in overall survival, and differences in responses to drugs. Therefore, prognostic and predictive biomarkers are needed to guide treatment decisions. To develop the most effective immunotherapeutic strategies for mCRPC, it is essential to dissect tumor immunogenicity, immune infiltration, and immune escape in each tumor. However, to date very little is known about the role of adaptive and innate immunity in mCRPC and their association with survival. The central hypothesis of this research is that immune phenotypes, such as tumor infiltrating lymphocytes TILs and immune checkpoints, are important predictors of survival in mCRPC. Further, we hypothesize that mCRPC patients with better outcomes will be characterized by a stronger and more diverse immune phenotype that is in general associated with better responses to immunotherapy. Therefore, the overarching goal of this research is to dissect signatures of immune infiltration and escape in mCRPC and to identify novel mechanistic biomarkers of cancer immune evasion. The successful completion of this work will result in the first comprehensive immunogenomic landscape of mCRPC. Further, we will characterize mechanisms of immune evasion e.g. immune-checkpoints in mCRPC and their association with survival. Our work established critical dependencies between the genotypes of mCRPCs and their phenotypes. These genotype-phenotype relationships are then used to identify prognostic biomarkers, which is the foundation for accurate patient stratifications in the paradigm of personalized medicine. Hence, our work augments the precision oncology with an actionable perspective on the tumor immune microenvironment.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research