NDLI: Mesothelin-specific CD 8 T Cell Responses Provide Evidence of In Vivo Cross-Priming by Antigen-Presenting Cells in Vaccinated Pancreatic Cancer Patients

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Mesothelin-specific CD 8 T Cell Responses Provide Evidence of In Vivo Cross-Priming by Antigen-Presenting Cells in Vaccinated Pancreatic Cancer Patients

Content Provider	Semantic Scholar
Author	Thomas, Amy Morck Santarsiero, Lynn M. Lutz, Eric R. Armstrong, Todd D. Chen, Yi-Cheng Huang, Lan-Qing Laheru, Daniel A. Goggins, Michael Hruban, Ralph H. Jaffee, Elizabeth M.
Copyright Year	2004
Abstract	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.
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://jem.rupress.org/content/jem/200/3/297.full.pdf
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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