Broad cross-presentation of the hematopoietically derived PR1 antigen on solid tumors leads to susceptibility to PR1-targeted immunotherapy.
Broad cross-presentation of the hematopoietically derived PR1 antigen on solid tumors leads to susceptibility to PR1-targeted immunotherapy.
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DOI：
10.4049/jimmunol.1201221
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发表时间：
2012-12-01
期刊：
影响因子：
--
通讯作者：
Molldrem JJ
中科院分区：
文献类型：
--
作者：
Alatrash G;Mittendorf EA;Sergeeva A;Sukhumalchandra P;Qiao N;Zhang M;St John LS;Ruisaard K;Haugen CE;Al-Atrache Z;Jakher H;Philips AV;Ding X;Chen JQ;Wu Y;Patenia RS;Bernatchez C;Vence LM;Radvanyi LG;Hwu P;Clise-Dwyer K;Ma Q;Lu S;Molldrem JJ
PR1 是一种人类白细胞抗原 (HLA)-A2 限制肽，已通过免疫疗法成功靶向治疗髓性白血病。 PR1 源自中性粒细胞颗粒蛋白酶 3 (P3) 和中性粒细胞弹性蛋白酶 (NE)，两者均存在于肿瘤微环境中。我们最近表明，P3 和 NE 被正常和白血病来源的抗原呈递细胞摄取并交叉呈递，并且 NE 被乳腺癌细胞摄取。现在，我们扩展了我们的研究结果，表明 P3 和 NE 被人类实体瘤摄取并交叉呈递。我们进一步表明，PR1 交叉呈递使人乳腺癌和黑色素瘤细胞容易被 PR1 特异性细胞毒性 T 淋巴细胞 (PR1-CTL) 和抗 PR1/HLA-A2 抗体 8F4 杀死。我们还显示了乳腺癌和黑色素瘤患者外周血中的 PR1-CTL。总之，我们的数据将交叉呈递确定为一种新机制，通过该机制，缺乏抗原内源表达的细胞变得对针对交叉呈递抗原的疗法敏感，并表明 PR1 是一种广泛表达的肿瘤抗原。
PR1 is a human leukocyte antigen (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 antigen presenting cells, 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 cytotoxic T lymphocytes (PR1-CTL) and the anti-PR1/HLA-A2 antibody 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 antigen become susceptible to therapies that target cross-presented antigens and suggest PR1 as a broadly expressed tumor antigen.
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影响因子：
11.2
作者：
Mittendorf EA;Alatrash G;Qiao N;Wu Y;Sukhumalchandra P;St John LS;Philips AV;Xiao H;Zhang M;Ruisaard K;Clise-Dwyer K;Lu S;Molldrem JJ
通讯作者：
Molldrem JJ
影响因子：
4.4
作者：
Burgdorf, Sven;Lukacs-Kornek, Veronika;Kurts, Christian
通讯作者：
Kurts, Christian
影响因子：
56.9
作者：
KOVACSOVICSBANKOWSKI, M;ROCK, KL
通讯作者：
ROCK, KL
影响因子：
45.3
作者：
Jensen, Hanne Krogh;Donskov, Frede;von der Maase, Hans
通讯作者：
von der Maase, Hans
影响因子：
6.4
作者：
Desmedt, Christine;El Ouriaghli, Frank;Sotiriou, Christos
通讯作者：
Sotiriou, Christos