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Project

Facilitating immuotherapy responses in non-T cell-inflamed bladder cancer

Funder: American Association For Cancer Research

Funding period
USD 110 K
Funding amount
Abstract
Muscle invasive urothelial bladder cancer is a lethal disease with few novel FDA-approved therapies over the past 20 years. Bladder cancer possesses a high mutational burden and antigenicity, yet is able to prevent and evade an anti-tumor immune response. Recently, anti-PD-L1 therapy was approved for metastatic bladder cancer based on impressive and durable responses in a subset of patients. Yet most patients’ tumors still do not respond to immune checkpoint blockade. Mechanisms of immune resistance in bladder cancer remain poorly understood. T cell infiltration has been associated with improved survival and response to immunotherapy. My recent work has focused on discovering of oncogenic pathways linked with the non-T cell inflamed tumor microenvironment. The focus of this proposal is on further understanding this immune subtype, to better circumvent mechanisms of immune resistance in UBC. Since we recently discovered that FGFR3 mutations are exclusively mutated in non-T cell-inflamed tumors, this proposal will aim to mechanistically elucidate whether activation of this pathway is causally related to T cell exclusion and responsible for anti-PD-1/PD-L1 resistance. To investigate this question, both human tissue samples and preclinical laboratory modeling will be used. Finally, I will also explore publicly available genomic data sets to identify additional oncogenic pathways that may lead to T cell exclusion, which may serve as the subject subject of future experimental evaluation.
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System

Categories
  • FOR (ANZSRC)

    1107 Immunology

  • FOR (ANZSRC)

    1112 Oncology and Carcinogenesis

  • RCDC

    Biotechnology

  • RCDC

    Cancer

  • RCDC

    Clinical Research

  • RCDC

    Immunization

  • RCDC

    Urologic Diseases

  • HRCS HC

    Cancer

  • HRCS RAC

    2.1 Biological and endogenous factors

  • HRCS RAC

    5.1 Pharmaceuticals

  • Health Research Areas

    Biomedical

  • Broad Research Areas

    Basic Science