4.8 Article

Identification of class I MHC-associated phosphopeptides as targets for cancer immunotherapy

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NATL ACAD SCIENCES
DOI: 10.1073/pnas.0604045103

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tandem mass spectrometry; immobilized metal-affinity chromatography

资金

  1. NCI NIH HHS [R01 CA134060] Funding Source: Medline
  2. NIAID NIH HHS [R37 AI020963, R37 AI033993, AI 33993, R01 AI033993, R01 AI020963, AI 20963] Funding Source: Medline

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Alterations in phosphorylation of cellular proteins are a hallmark of malignant transformation. Degradation of these phosphoproteins could generate cancer-specific class I MHC-associated phosphopepticles recognizable by CD8(+) T lymphocytes. In a comparative analysis of phosphopeptides presented on the surface of melanoma, ovarian carcinoma, and B lymphoblastoid cells, we find 5 of 36 that are restricted to the solid tumors and common to both cancers. Differential presentation of these peptides can result from differential phosphorylation of the source proteins. Recognition of the peptides on cancer cells by phosphopepticle-specific CD8(+) T lymphocytes validates the potential of these phosphopeptides as immunotherapeutic targets.

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