Whereas virtually any antigen expressing MHC class I+ cell can present tumor antigens to CD8+ T cells, only professional antigen-presenting cells (APC) have the capacity to prime tumor antigen specific naïve CD8+ T cells in vivo. Professional APC can acquire exogenous tumor antigens and present them via their own MHC class I molecules to CD8+ T cells in a process known as antigen cross-presentation (1). The precise molecular pathways leading to cross-priming, however, remain controversial (2), and even the relevance of tumor antigen cross-presentation for the induction of anti-tumor responses has been questioned (3-5). In this presentation, I will review the proposed molecular basis for cross-presentation, the APC subsets which are known to be involved in this phenomenon and the in vivo conditions which may result in cross-priming of tumor antigen specific CD8+ T cells versus cross-tolerance. I will then show recent evidence that vaccination of cancer patients with NY-ESO-1 recombinant protein, Montanide® ISA-51 and the TLR9 ligand CpG 7909, can result in the in vivo cross-priming of NY-ESO-1 specific CD8+ T cells able to recognize endogenously expressed NY-ESO-1 antigen, indicating that cross-presentation of tumor antigens is highly relevant for tumor immunotherapy and can occur, following activation of professional APC, in the presence of appropriate levels of integrated humoral and CD4+ T-cell responses. The presented data provide direct evidence of in vivo cross-priming of specific CD8+ T cells by a recombinant full-length tumor antigen vaccine in cancer patients and support the use of this type of formulation for the further development of efficient cancer vaccines.
This abstract was published in Cancer Immunity, a Cancer Research Institute journal that ceased publication in 2013 and is now provided online in association with Cancer Immunology Research.
- Copyright © 2007 by Danila Valmori