Accession Number:

ADA566916

Title:

Identifying a Defective Pathway in Innate Immunity as an Immunoescape Mechanism for Breast Cancer Development

Descriptive Note:

Final rept. 1 Apr 2011-31 Mar 2012

Corporate Author:

MIAMI UNIV FL

Personal Author(s):

• Barber, Glen

Report Date:

2012-04-01

Pagination or Media Count:

5.0

Abstract:

The innate immune system is critical for the early detection of invading pathogens and for initiating cellular host defense counter measures, which include the production of type I interferon IFN. Immune dysfunction develops in patients with many cancer types and may contribute to tumor progression and failure of immunotherapy. This study will investigate the role of a newly identified IFN-mediated innate immunity pathway in immune surveillance, and the inactivation of a critical component of the pathway, STING, as a mechanism for immuo-escape in the development and progression of breast cancer. We propose a pilot study to test this hypothesis, that innate immunity pathway involved STING plays a role in purging pre-neoplastic cells and suppression of STING is a mechanism for escape of breast cancer cells from immune surveillance. Over the course of the study, we determined that STING was absent from many human breast cancer cell lines, at both the RNA and protein level. This caused the lack of IFN beta secretion in response to intracellular DNA. In human breast cancer tissue, we observed the presence of human retroviral elements and up-regulation of a number of immune response genes, as compared to normal human tissue.

Descriptors:

• *BREAST CANCER
• DYSFUNCTION
• GENETICS
• IMMUNITY
• NEOPLASMS
• PATHOGENIC MICROORGANISMS
• RIBONUCLEIC ACIDS
• TISSUES(BIOLOGY)

Subject Categories:

• Anatomy and Physiology
• Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE