Mesothelin-specific CD8+ T Cell Responses Provide Evidence of In Vivo Cross-Priming by Antigen-Presenting Cells in Vaccinated Pancreatic Cancer Patients
| Autor: | Ralph H. Hruban, Lynn M. Santarsiero, Elizabeth M. Jaffee, Michael Goggins, Eric R. Lutz, Lan Qing Huang, Daniel A. Laheru, Yi-Cheng Chen, Todd D. Armstrong, Amy Morck Thomas |
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| Rok vydání: | 2004 |
| Předmět: |
T cell
Immunology Antigen presentation T lymphocytes Antigen-Presenting Cells Priming (immunology) CD8-Positive T-Lymphocytes HLA-A3 Antigen GPI-Linked Proteins Major histocompatibility complex Cancer Vaccines Article Cell Line 03 medical and health sciences antigen 0302 clinical medicine Antigen HLA-A2 Antigen Humans Immunology and Allergy Cytotoxic T cell Medicine Hypersensitivity Delayed Antigen-presenting cell 030304 developmental biology 0303 health sciences Membrane Glycoproteins biology business.industry Vaccination Granulocyte-Macrophage Colony-Stimulating Factor epitopes 3. Good health Pancreatic Neoplasms medicine.anatomical_structure Mesothelin biology.protein immunotherapy cancer vaccine business CD8 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20031435 |
| Popis: | Tumor-specific CD8+ T cells can potentially be activated by two distinct mechanisms of major histocompatibility complex class I–restricted antigen presentation as follows: direct presentation by tumor cells themselves or indirect presentation by professional antigen-presenting cells (APCs). However, controversy still exists as to whether indirect presentation (the cross-priming mechanism) can contribute to effective in vivo priming of tumor-specific CD8+ T cells that are capable of eradicating cancer in patients. A clinical trial of vaccination with granulocyte macrophage–colony stimulating factor–transduced pancreatic cancer lines was designed to test whether cross-presentation by locally recruited APCs can activate pancreatic tumor-specific CD8+ T cells. Previously, we reported postvaccination delayed-type hypersensitivity (DTH) responses to autologous tumor in 3 out of 14 treated patients. Mesothelin is an antigen demonstrated previously by gene expression profiling to be up-regulated in most pancreatic cancers. We report here the consistent induction of CD8+ T cell responses to multiple HLA-A2, A3, and A24-restricted mesothelin epitopes exclusively in the three patients with vaccine-induced DTH responses. Importantly, neither of the vaccinating pancreatic cancer cell lines expressed HLA-A2, A3, or A24. These results provide the first direct evidence that CD8 T cell responses can be generated via cross-presentation by an immunotherapy approach designed to recruit APCs to the vaccination site. |
| Databáze: | OpenAIRE |
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