Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/47508
Title: DNA DAMAGE RESPONSE INDUCES ANTIGEN PRESENTING CELL-LIKE FUNCTIONS IN FIBROBLASTS
Authors: TANG LI FANG MELISSA
Keywords: DNA damage response, adaptive immunity, APC, DNAM-1, ICAM-1,
Issue Date: 17-Jan-2013
Source: TANG LI FANG MELISSA (2013-01-17). DNA DAMAGE RESPONSE INDUCES ANTIGEN PRESENTING CELL-LIKE FUNCTIONS IN FIBROBLASTS. ScholarBank@NUS Repository.
Abstract: The ATM/ATR-initiated DNA damage response (DDR) upregulates expression of major histocompatibility complex (MHC) class I molecules and ligands for the activating immune receptors NKG2D, DNAM-1 and LFA-1 on fibroblasts. Here we provide evidence that OVA257-264-pulsed fibroblasts gain the ability to activate naïve OT-I CD8+ T cells in response to DNA damage. Stimulation of naïve CD8+ T cells critically depended on DNAM-1 expression on T cells and ICAM-1 and MHC class I expression on fibroblasts. OVA257-264-pulsed fibroblasts were able to induce a protective T cell response against B16-OVA cells. Our findings show that fibroblasts acquire antigen presenting-cell (APC)-like features in response to DNA damage. Fibroblasts can be genetically manipulated and efficiently expanded to potentially overcome the limitations of current dendritic cell-based immunotherapy protocols. In addition, we demonstrated an ATM dependent tumour immune surveillance in a spontaneous Eµ-myc induced B cell lymphoma tumour model. Overall, DDR in aberrant/tumour cells plays a direct role in activating the adaptive immune response.
URI: http://scholarbank.nus.edu.sg/handle/10635/47508
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