Regulation of the Prostate Cancer Tumor Microenvironment

Abstract

The role of innate immunity in prostate cancer tumorigenesis is unclear. Toll-like receptors (TLRs) are key signaling molecules that regulate innate and adaptive immune responses in the presence of pathogens and endogenous ligands. We have generated and begun to characterize TRAMP Tg(exp +/-) x MyD88' mice. Initial results reveal that de novo prostate cancers in absence of MyD88 develop higher grade adenocarcinomas than wild-type controls at 30 weeks of age. Analysis of tumor infiltrating cells at 24 and 30 weeks of age already reveal increased infiltration of macrophage lineage cells, decreased CD8 T lymphocytes, NK cells, as well as decreased activation of canonical NF- B levels and increased non-canonical NF- B levels in the MyD88-deficient TRAMP Tg(exp +/-) mice. We have also observed decreased splenocytic NK cells in MyD88(exp -/-) animals with and without the presence of prostate cancer. From these data, we will determine the role of the MyD88 pathway of innate immunity in prostate cancer tumorigenesis. However, we have noted several limitations of our current system in achieving our initial aims. Thus, we have also proposed and now have been approved a revised SOW.

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Document Details

Document Type
Technical Report
Publication Date
Apr 01, 2014
Accession Number
ADA601302

Entities

People

  • Arnold I. Chin

Organizations

  • University of California, Los Angeles

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Blood
  • Cancer
  • Cells
  • Chemistry
  • Diseases And Disorders
  • Genetics
  • Immune System
  • Immunity
  • Lymphocytes
  • Molecules
  • Myeloid Cells
  • Neoplasms
  • Prostate Cancer
  • Proteins
  • T Lymphocytes
  • Therapy

Fields of Study

  • Biology
  • Medicine

Readers

  • Immunology
  • Molecular and genetic basis of cancer.
  • Oncology (Cancer Research).