Absence of scavenger receptor A promotes dendritic cell-mediated cross-presentation of cell-associated antigen and antitumor immune response

Immunol Cell Biol. 2012 Jan;90(1):101-8. doi: 10.1038/icb.2011.10. Epub 2011 Mar 8.


Given the primary expression of scavenger receptor A (SRA) or CD204 on antigen-presenting cells, we investigate the immunoregulatory activities of SRA/CD204 in the context of cross-presentation of cell-associated antigen and the immunogenicity of dying tumor cells. Immunization with dying prostate cancer cells results in profoundly increased control of subsequently inoculated tumors in SRA/CD204 knockout mice. Using OVA-expressing RM1 prostate tumor line (RM1-OVA), we show for the first time that SRA absence greatly enhances dendritic cells (DCs)-mediated cross-presentation of OVA antigen derived from dying RM1 cells. While the phagocytic ability of DCs is not significantly impacted by the lack of SRA/CD204, DCs deficient in SRA/CD204 display increased expression of inflammatory cytokines and chemokines, as well as co-stimulatory molecules upon interaction with dying RM1 cells, implicating a suppressive regulation of the functional activation of DCs by SRA/CD204. Further, SRA/CD204-deficient DCs pulsed with dying RM1-OVA cells are more effective than wild-type counterparts in priming antigen-specific T-cell responses, resulting in improved control of RM1 tumor growth in both prophylactic and therapeutic settings. Our findings suggest that the increased immunogenicity of dying tumor cells in SRA/CD204 knockout mice is attributed to the altered functions of DCs in the absence of SRA/CD204, which underscores the important role of SRA/CD204 in host immune homeostasis. Selective downregulation or blockade of this immunoregulatory molecule may lead to enhanced potency of DC-based vaccines capable of breaking immune tolerance against cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Antigens / genetics
  • Antigens / immunology*
  • Antigens / metabolism
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Cell Line, Tumor
  • Cells, Cultured
  • Cross-Priming / immunology*
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / transplantation
  • Flow Cytometry
  • Immunotherapy, Adoptive / methods
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasms, Experimental / immunology*
  • Neoplasms, Experimental / pathology
  • Neoplasms, Experimental / therapy
  • Ovalbumin / genetics
  • Ovalbumin / immunology
  • Ovalbumin / metabolism
  • Phagocytosis / immunology
  • Scavenger Receptors, Class A / deficiency
  • Scavenger Receptors, Class A / genetics
  • Scavenger Receptors, Class A / immunology*
  • Tumor Burden / genetics
  • Tumor Burden / immunology


  • Antigens
  • Cytokines
  • Inflammation Mediators
  • Msr1 protein, mouse
  • Scavenger Receptors, Class A
  • Ovalbumin