Combining Androgen Deprivation and Immunotherapy to Prevent Progression to Castration-Resistant Prostate Cancer
Abstract
Recently, we found that in a PTEN-deficient mouse PCa model, castration induces an immunosuppressive state within the tumor that is concurrent with tumor recurrence. Mechanistically, this response to ADT is mediated by soluble mediators (TNF and CCL2), facilitating communication between tumor, stromal and immune cell populations within the tumor microenvironment. Based on these preliminary data, we hypothesize: Blocking myeloid suppression prevents progression to castration resistant prostate cancer. We test this hypothesis in three aims. Aim 1 examines the mechanism of paracrine TNF signaling between tumor, stromal and myeloid cell populations within the TME, in inducing immune suppression following ADT. Aim 2 tests whether blocking the transit and/or function of myeloid suppressive cell populations prevents CRPC (tumor recurrence following ADT). We also determine the role of PTEN in ADT-induced immune evasion. Aim 3 tests the hypothesis that ADT, in men with locally advanced PrCa, increases serum TNF and CCL2, as well as circulating myeloid cells, by assessing samples from an ongoing clinical study.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2021
- Accession Number
- AD1155733
Entities
People
- Bo Xu
- Chatta Gurkamal
- John J. Kroleewski
- Kent Nastiuk