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Scavenger Receptor-A Negatively Regulates Antitumor Immunity

Departments of ¹ Cellular Stress Biology, ² Urologic Oncology, and ³ Immunology, Roswell Park Cancer Institute, Buffalo, New York

Requests for reprints: Xiang-Yang Wang, Department of Cellular Stress Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263. Phone: 716-845-2375; E-mail: xiang-yang.wang{at}roswellpark.org.

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. [Cancer Res 2007;67(10):4996–5002]

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