Nonclassical antigen-processing pathways are required for MHC class II-restricted direct tumor recognition by NY-ESO-1-specific CD4(+) T cells Journal Article


Authors: Matsuzaki, J.; Tsuji, T.; Luescher, I.; Old, L. J.; Shrikant, P.; Gnjatic, S.; Odunsi, K.
Article Title: Nonclassical antigen-processing pathways are required for MHC class II-restricted direct tumor recognition by NY-ESO-1-specific CD4(+) T cells
Abstract: Tumor antigen-specific CD4(+) T cells that directly recognize cancer cells are important for orchestrating antitumor immune responses at the local tumor sites. However, the mechanisms of direct MHC class II (MHC-II) presentation of intracellular tumor antigen by cancer cells are poorly understood. We found that two functionally distinct subsets of CD4(+) T cells were expanded after HLA-DPB1*04 (DP04)-binding NY-ESO-1(157-170) peptide vaccination in patients with ovarian cancer. Although both subsets recognized exogenous NY-ESO-1 protein pulsed on DP04(+) target cells, only one type recognized target cells with intracellular expression of NY-ESO-1. The tumor-recognizing CD4(+) T cells more efficiently recognized the short 8-9-mer peptides than the non-tumor-recognizing CD4(+) T cells. In addition to endosomal/lysosomal proteases that are typically involved in MHC-II antigen presentation, several pathways in the MHC class I presentation pathways, such as the proteasomal degradation and transporter-associated with antigen-processing-mediated peptide transport, were also involved in the presentation of intracellular NY-ESO-1 on MHC-II. The presentation was inhibited significantly by primaquine, a small molecule that inhibits endosomal recycling, consistent with findings that pharmacologic inhibition of new protein synthesis enhances antigen presentation. Together, our data demonstrate that cancer cells selectively present peptides from intracellular tumor antigens on MHC-II by multiple nonclassical antigen-processing pathways. Harnessing the direct tumor-recognizing ability of CD4(+) T cells could be a promising strategy to enhance antitumor immune responses in the immunosuppressive tumor microenvironment. (C) 2013 AACR.
Keywords: melanoma; protein; peptide; dendritic cells; hsp90; ovarian-cancer; nuclear antigen; ny-eso-1; molecules; cross-presentation
Journal Title: Cancer Immunology Research
Volume: 2
Issue: 4
ISSN: 2326-6066
Publisher: American Association for Cancer Research  
Date Published: 2014-04-01
Start Page: 341
End Page: 350
Language: English
ACCESSION: WOS:000340033600009
DOI: 10.1158/2326-6066.cir-13-0138
PROVIDER: wos
PMCID: PMC4004114
PUBMED: 24764581
Notes: Article -- Source: Wos
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MSK Authors
  1. Sacha Gnjatic
    111 Gnjatic
  2. Takemasa Tsuji
    14 Tsuji
  3. Lloyd J Old
    381 Old