Broad cross-presentation of the hematopoietically derived PR1 antigen on solid tumors leads to susceptibility to PR1-targeted immunotherapy

Gheath Alatrash, Elizabeth A. Mittendorf, Anna Sergeeva, Pariya Sukhumalchandra, Na Qiao, Mao Zhang, Lisa S. St John, Kathryn Ruisaard, Christine E. Haugen, Zein Al-Atrache, Haroon Jakher, Anne V. Philips, Xiaoling Ding, Jie Qing Chen, Yun Wu, Rebecca S. Patenia, Chantale Bernatchez, Luis M. Vence, Laszlo G. Radvanyi, Patrick HwuKaren Clise-Dwyer, Qing Ma, Sijie Lu, Jeffrey J. Molldrem

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5476-5484
Number of pages9
JournalJournal of Immunology
Volume189
Issue number11
DOIs
StatePublished - Dec 1 2012

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

MD Anderson CCSG core facilities

  • Monoclonal Antibody Facility
  • Advanced Technology Genomics Core
  • Flow Cytometry and Cellular Imaging Facility
  • Tissue Biospecimen and Pathology Resource
  • Cytogenetics and Cell Authentication Core

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