Characterization of Neoantigens in Hepatocellular Carcinoma Patients Enrolled on Immunotherapy
DescriptionSuccessful treatment of cancers with Immune Checkpoint Inhibitors (ICls) has been associated with the mutational load of tumors. The biological rationale for this association between mutational load and ICI response is that neoantigens are generated by mutations in protein coding sequences that provide a steady flow of neoantigens to prime the immune system for the production of antigen-specific tumor-infiltrating lymphocytes (Tlls). There are additional sets of undiscovered neoantigens that bind to patient's HLA and can be recognized by TIL, i.e. cancerspecific, alternatively spliced epitopes that function as neoantigens. We propose to use full-length Single Molecule Real Time (SMRT) RNA-seq to uncover pathologically spliced mRNAs in hepatocellular carcinoma (HCC) samples. The findings under this proposal will have a significant impact on our understanding of antigenicity in cancer and possibly other diseases and the approach to immunotherapy including adoptive T-cell transfer.
|Effective start/end date||1/02/20 → …|