First Author | Wang XY | Year | 2007 |
Journal | Cancer Res | Volume | 67 |
Issue | 10 | Pages | 4996-5002 |
PubMed ID | 17510431 | Mgi Jnum | J:121736 |
Mgi Id | MGI:3711399 | Doi | 10.1158/0008-5472.CAN-06-3138 |
Citation | Wang XY, et al. (2007) Scavenger receptor-A negatively regulates antitumor immunity. Cancer Res 67(10):4996-5002 |
abstractText | The scavenger receptor-A (SR-A), originally recognized by its ability to internalize modified lipoproteins, has largely been studied in relation to atherosclerosis as well as innate immunity against pathogen infection. SR-A was recently shown to be a receptor on antigen-presenting cell for heat shock protein (HSP) and was implicated in the cross-presentation of HSP-chaperoned antigens. Here, we show that SR-A is not required for antitumor immunity generated by HSP-based (e.g., grp170) vaccine approaches in vivo. The lack of SR-A significantly enhances HSP- or lipopolysaccharide-mediated vaccine activities against poorly immunogenic tumors, indicating that SR-A is able to attenuate immunostimulatory effects of adjuvants or 'danger' molecules. The improved antitumor response in SR-A knockout mice is correlated with an increased antigen-specific T-cell response. Moreover, SR-A-deficient dendritic cells are more responsive to inflammatory stimuli and display a more effective antigen-presenting capability compared with wild-type cells. This is the first report illustrating that SR-A negatively regulates antigen-specific antitumor immunity, which has important clinical implications in vaccine design for cancer immunotherapy. |