MHC class I-associated phosphopeptides are the targets of memory-like immunity in leukemia

Research output: Contribution to journalArticle

Authors

  • Andrew Norris
  • Joy M Polefrone
  • Jie Qian
  • Ann Michelle English
  • Kara L Cummings
  • Jennifer Cottine
  • Jennifer G Abelin
  • Stacy A Malaker
  • Angela L Zarling
  • Hsing-Wen Huang
  • Sylvie Freeman
  • Jeffrey Shabanowitz
  • Dickens Pratt
  • Charles Craddock
  • Michael E Williams
  • Donald F Hunt
  • Victor H Engelhard

Abstract

Deregulation of signaling pathways is a hallmark of malignant transformation. Signaling-associated phosphoproteins can be degraded to generate cancer-specific phosphopeptides that are presented by major histocompatibility complex (MHC) class I and II molecules and recognized by T cells; however, the contribution of these phosphoprotein-specific T cells to immune surveillance is unclear. We identified 95 phosphopeptides presented on the surface of primary hematological tumors and normal tissues, including 61 that were tumor-specific. Phosphopeptides were more prevalent on more aggressive and malignant samples. CD8(+) T cell lines specific for these phosphopeptides recognized and killed both leukemia cell lines and human leukocyte antigen-matched primary leukemia cells ex vivo. Notably, healthy individuals showed robust CD8(+) T cell responses against many of these phosphopeptides within the circulating memory compartment. This immunity was significantly reduced or absent in some leukemia patients. This reduction correlated with clinical outcome; however, immunity was restored after allogeneic stem cell transplantation. These results suggest that phosphopeptides may be targets of cancer immune surveillance in humans, and point to their importance for development of vaccine-based and T cell adoptive transfer immunotherapies.

Details

Original languageEnglish
Pages (from-to)203ra125
JournalScience Translational Medicine
Volume5
Issue number203
Publication statusPublished - 18 Sep 2013

Keywords

  • CD8-Positive T-Lymphocytes, Cells, Cultured, Humans, Immunity, Leukemia, Major Histocompatibility Complex, Phosphopeptides, T-Lymphocytes