학술논문
Broad Cross-Presentation of the Hematopoietically Derived PR1 Antigen on Solid Tumors Leads to Susceptibility to PR1-Targeted Immunotherapy.
Document Type
Article
Author
Alatrash, Gheath; Mittendorf, Elizabeth A.; Sergeeva, Anna; Sukhumalchandra, Pariya; Na Qiao; Mao Zhang; John, Lisa S. St.; Ruisaard, Kathryn; Haugen, Christine E.; Al-Atrache, Zein; Jakher, Haroon; Philips, Anne V.; Ding, Xiaoling; Jie Qing Chen; Yun Wu; Patenia, Rebecca S.; Bernatchez, Chantale; Vence, Luis M.; Radvanyi, Laszlo G.; Hwu, Patrick
Source
Subject
*HEMATOPOIESIS
*DISEASE susceptibility
*HLA histocompatibility antigens
*MYELOID leukemia
*CANCER immunotherapy
*PROTEOLYTIC enzymes
*LEUCOCYTE elastase
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Language
ISSN
0022-1767
Abstract
PRl is a HLA-A2-restricted peptide that has been targeted successfully in myeloid leukemia with immunotherapy. PR1 is derived from the neutrophil granule proteases proteinase 3 (P3) and neutrophil elastase (NE), which are both found in the tumor microenvironment. We recently showed that P3 and NE are taken up and cross-presented by normal and leukemia-derived APCs, and that NE is taken up by breast cancer cells. We now extend our findings to show that P3 and NE are taken up and cross-presented by human solid tumors. We further show that PRl cross-presentation renders human breast cancer and melanoma cells susceptible to killing by PRl-specific CTLs (PR1-CTL) and the anti-PRl/HLA-A2 Ab 8F4. We also show PR1-CTL in peripheral blood from patients with breast cancer and melanoma. Together, our data identify cross-presentation as a novel mechanism through which cells that lack endogenous expression of an Ag become susceptible to therapies that target cross-presented Ags and suggest PRl as a broadly expressed tumor Ag. [ABSTRACT FROM AUTHOR]