Impaired tumor antigen processing by immunoproteasome-expressing CD40-activated B cells and dendritic cells

Karen S. Anderson, Wanyong Zeng, Tetsuro Sasada, Jaewon Choi, Angelika B. Riemer, Mei Su, Donna Drakoulakos, Yoon Joong Kang, Vladimir Brusic, Catherine Wu, Ellis L. Reinherz

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Professional APCs, such as dendritic cells, are routinely used in vitro for the generation of cytotoxic T lymphocytes specific for tumor antigens. In addition to dendritic cells, CD40-activated B cells and variant K562 leukemic cells can be readily transfected with nucleic acids for in vitro and in vivo antigen presentation. However, the expression of immunoproteasome components in dendritic cells may preclude display of tumor antigens such as Mart1/MelanA. Here, we use three target epitopes, two derived from tumor antigens [Mart1 26-34 (M26) and Cyp1B1239-247 (Cyp239)] and one derived from the influenza A viral antigen [FluM158-66 (FluM58)], to demonstrate that CD40-activated B cells, like dendritic cells, have a limited capability to process certain tumor antigens. In contrast, the K562 HLA-A*0201 transfectant efficiently processes and presents M26 and Cyp239 as well as the influenza FluM58 epitopes to T cells. These results demonstrate that the choice of target APC for gene transfer of tumor antigens may be limited by the relative efficacy of proteasome components to process certain tumor epitopes. Importantly, K562 can be exploited as an artificial APC, efficient in processing both M26 and Cyp239 epitopes and presumably, by extension, other relevant tumor antigens.

Original languageEnglish
Pages (from-to)857-867
Number of pages11
JournalCancer Immunology, Immunotherapy
Volume60
Issue number6
DOIs
Publication statusPublished - Jun 2011

Keywords

  • Antigen processing
  • Dendritic cells
  • Tumor immunity
  • Vaccination

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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