Accession Number : ADA597797


Title :   Reversing Breast Cancer-Induced Immune Suppression


Descriptive Note : Annual summary 15 Dec 2012-14 Dec 2013


Corporate Author : MARYLAND UNIV BALTIMORE


Personal Author(s) : Beury, Daniel W ; Ostrand-Rosenberg, Suzanne


Full Text : http://www.dtic.mil/get-tr-doc/pdf?AD=ADA597797


Report Date : Jan 2014


Pagination or Media Count : 10


Abstract : Previous studies have shown that MDSC block adaptive anti-tumor immunity by producing high levels of oxidizing agents such as reactive oxygen species (ROS), nitric oxide (NO), and peroxynitrite. Despite high levels of the toxic oxidizing agents, MDSC survive and suppress anti-tumor immunity. We hypothesize that MDSC survival is mediated by the antioxidant-regulating transcription factor Nrf2. To test this hypothesis, wild type and Nrf2-/- BALB/c and C57BL/6 mice were injected with 4T1 mammary carcinoma cells or MC38 colon carcinoma cells, respectively. Tumor-bearing mice were assayed weekly for percentage of MDSC in the blood and for MDSC levels of ROS and glutathione, MDSC production of H2O2 and suppressive activity, and MDSC apoptosis. Mice were also followed for survival. Nrf2-/- MDSC had more ROS and less glutathione than wild type MDSC, indicating that Nrf2-/- MDSC were more oxidatively stressed. Nrf2-/- MDSC were more apoptotic than wild type MDSC. Nrf2-/- and wild type mice had similar rates of primary tumor growth and MDSC accumulation, but tumor-bearing Nrf2-/- mice lived longer, indicating that Nrf2 contributes to tumor progression. Nrf2-/- MDSC produce less H2O2 and were less suppressive than wild type MDSC. These data are consistent with our hypothesis that Nrf2 regulates MDSC survival and suppressive activity, resulting in less suppressive MDSC in Nrf2-/- mice, thereby increasing anti-tumor immunity against metastatic disease.


Descriptors :   *BREAST CANCER , NEOPLASMS , NITRIC OXIDE , OXYGEN , SUPPRESSION


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE