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Marginating dendritic cells of the tumor microenvironment cross-present tumor antigens and stably engage tumor-specific T cells.

Cancer cell | Mar 20, 2012

http://www.ncbi.nlm.nih.gov/pubmed/22439936

The nature and site of tumor-antigen presentation to immune T cells by bone-marrow-derived cells within the tumor microenvironment remains unresolved. We generated a fluorescent mouse model of spontaneous immunoevasive breast cancer and identified a subset of myeloid cells with significant similarity to dendritic cells and macrophages that constitutively ingest tumor-derived proteins and present processed tumor antigens to reactive T cells. Using intravital live imaging, we determined that infiltrating tumor-specific T cells engage in long-lived interactions with these cells, proximal to the tumor. In vitro, these cells capture cytotoxic T cells in signaling-competent conjugates but do not support full activation or sustain cytolysis. The spatiotemporal dynamics revealed here implicate nonproductive interactions between T cells and antigen-presenting cells on the tumor margin.

Pubmed ID: 22439936 RIS Download

Mesh terms: Animals | Antigen Presentation | Antigens, Neoplasm | Breast Neoplasms | Cross-Priming | Dendritic Cells | Female | Humans | Lymphocyte Activation | Mice | Myeloid Cells | T-Lymphocytes | Tumor Microenvironment

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Associated grants

  • Agency: NCI NIH HHS, Id: CA108462
  • Agency: NCI NIH HHS, Id: R01 CA134622
  • Agency: NCI NIH HHS, Id: R01 CA134622-01A1
  • Agency: NCI NIH HHS, Id: R01CA129523
  • Agency: NCI NIH HHS, Id: R01CA134622
  • Agency: NCI NIH HHS, Id: U01 CA141451
  • Agency: NCI NIH HHS, Id: U01 CA141451-01
  • Agency: NCI NIH HHS, Id: U01CA141451

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