The way in which tumor cells die is proposed to have a substantial impact on the generation of adaptive immune responses. In our previous studies we have been able to demonstrate that induction of apoptosis versus necrosis in subcutaneously growing tumors has profoundly different effects on tumor specific CD8+ T cells. While apoptotic tumor cell death promote anti-tumor immune responses necrotic tumor cell death impair these responses. Based on these in vivo findings we have been able to establish an in vitro system, which allows to dissect the immunological mechanisms responsible for these observations in more detail. We have been able to dissect on a molecular level how antigens from dying cells are being cross-presented by professional antigen presenting cells such as dendritic cells in vitro. More importantly we have identified different proteins, which either support or impair the presentation of antigens from dying cells. Ultimately our findings will help enhance immune responses against cancer cells

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC011258-02
Application #
8349429
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2011
Total Cost
$279,671
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Gamrekelashvili, Jaba; Ormandy, Lars A; Heimesaat, Markus M et al. (2012) Primary sterile necrotic cells fail to cross-prime CD8(+) T cells. Oncoimmunology 1:1017-1026