Immune checkpoint inhibitors have not been effective for immunologically “cold” tumors, such as prostate cancer, which contain scarce tumor infiltrating lymphocytes. We hypothesized that select tissue-specific and immunostimulatory bacteria can potentiate these immunotherapies. Here we show that a patient-derived prostate-specific microbe, CP1, in combination with anti-PD-1 immunotherapy, increased survival and decreased tumor burden in orthotopic MYC- and PTEN-mutant prostate cancer models. CP1 administered intra-urethrally specifically homed to and colonized tumors without causing any systemic toxicities. CP1 increased immunogenic cell death of cancer cells, T cell cytotoxicity, and tumor infiltration by activated CD8 and Th17 T cells, mature dendritic cells, M1 macrophages, and NK cells. CP1 also decreased intra-tumoral regulatory T cells and VEGF. Mechanistically, blocking CP1-recruited T cells from infiltrating the tumor inhibited its therapeutic efficacy. CP1 is a novel immunotherapeutic tool demonstrating how a tissue-specific microbe can increase tumor immunogenicity and sensitize an otherwise resistant cancer type to immunotherapy.

Last modified

• 04/22/2019

Creator

• Jonathan Forrest Anker

DOI

• https://doi.org/10.21985/N2SR3C

Subject

• Driskill Graduate Training Program in Life Sciences

Keyword

• Cancer

Date created

• 2018-01-01

Resource type

• Dissertation

Rights statement

• In Copyright