Multi-faceted immunomodulatory and tissue-tropic clinical bacterial isolate potentiates prostate cancer immunotherapy

Jonathan F. Anker, Anum F. Naseem, Hanlin Mok, Anthony J. Schaeffer, Sarki A. Abdulkadir () and Praveen Thumbikat ()
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Jonathan F. Anker: Northwestern University Feinberg School of Medicine
Anum F. Naseem: Northwestern University Feinberg School of Medicine
Hanlin Mok: Northwestern University Feinberg School of Medicine
Anthony J. Schaeffer: Northwestern University Feinberg School of Medicine
Sarki A. Abdulkadir: Northwestern University Feinberg School of Medicine
Praveen Thumbikat: Northwestern University Feinberg School of Medicine

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract 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, increases survival and decreases tumor burden in orthotopic MYC- and PTEN-mutant prostate cancer models. CP1 administered intra-urethrally specifically homes to and colonizes tumors without causing any systemic toxicities. CP1 increases immunogenic cell death of cancer cells, T cell cytotoxicity, and tumor infiltration by activated CD8 T cells, Th17 T cells, mature dendritic cells, M1 macrophages, and NK cells. CP1 also decreases intra-tumoral regulatory T cells and VEGF. Mechanistically, blocking CP1-recruited T cells from infiltrating the tumor inhibits its therapeutic efficacy. CP1 is an immunotherapeutic tool demonstrating how a tissue-specific microbe can increase tumor immunogenicity and sensitize an otherwise resistant cancer type to immunotherapy.

Date: 2018
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DOI: 10.1038/s41467-018-03900-x

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