TY - JOUR
T1 - Broad cross-presentation of the hematopoietically derived PR1 antigen on solid tumors leads to susceptibility to PR1-targeted immunotherapy
AU - Alatrash, Gheath
AU - Mittendorf, Elizabeth A.
AU - Sergeeva, Anna
AU - Sukhumalchandra, Pariya
AU - Qiao, Na
AU - Zhang, Mao
AU - St John, Lisa S.
AU - Ruisaard, Kathryn
AU - Haugen, Christine E.
AU - Al-Atrache, Zein
AU - Jakher, Haroon
AU - Philips, Anne V.
AU - Ding, Xiaoling
AU - Chen, Jie Qing
AU - Wu, Yun
AU - Patenia, Rebecca S.
AU - Bernatchez, Chantale
AU - Vence, Luis M.
AU - Radvanyi, Laszlo G.
AU - Hwu, Patrick
AU - Clise-Dwyer, Karen
AU - Ma, Qing
AU - Lu, Sijie
AU - Molldrem, Jeffrey J.
PY - 2012/12/1
Y1 - 2012/12/1
N2 - PR1 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 PR1 cross-presentation renders human breast cancer and melanoma cells susceptible to killing by PR1-specific CTLs (PR1-CTL) and the anti-PR1/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 PR1 as a broadly expressed tumor Ag.
AB - PR1 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 PR1 cross-presentation renders human breast cancer and melanoma cells susceptible to killing by PR1-specific CTLs (PR1-CTL) and the anti-PR1/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 PR1 as a broadly expressed tumor Ag.
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U2 - 10.4049/jimmunol.1201221
DO - 10.4049/jimmunol.1201221
M3 - Article
C2 - 23105141
AN - SCOPUS:84869847358
SN - 0022-1767
VL - 189
SP - 5476
EP - 5484
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -