Elevation of the TP53 isoform Δ133p53β in glioblastomas: an alternative to mutant p53 in promoting tumor development

J Pathol. 2018 Sep;246(1):77-88. doi: 10.1002/path.5111. Epub 2018 Jul 31.


As tumor protein 53 (p53) isoforms have tumor-promoting, migration, and inflammatory properties, this study investigated whether p53 isoforms contributed to glioblastoma progression. The expression levels of full-length TP53α (TAp53α) and six TP53 isoforms were quantitated by RT-qPCR in 89 glioblastomas and correlated with TP53 mutation status, tumor-associated macrophage content, and various immune cell markers. Elevated levels of Δ133p53β mRNA characterised glioblastomas with increased CD163-positive macrophages and wild-type TP53. In situ-based analyses found Δ133p53β expression localised to malignant cells in areas with increased hypoxia, and in cells with the monocyte chemoattractant protein C-C motif chemokine ligand 2 (CCL2) expressed. Tumors with increased Δ133p53β had increased numbers of cells positive for macrophage colony-stimulating factor 1 receptor (CSF1R) and programmed death ligand 1 (PDL1). In addition, cells expressing a murine 'mimic' of Δ133p53 (Δ122p53) were resistant to temozolomide treatment and oxidative stress. Our findings suggest that elevated Δ133p53β is an alternative pathway to TP53 mutation in glioblastoma that aids tumor progression by promoting an immunosuppressive and chemoresistant environment. Adding Δ133p53β to a TP53 signature along with TP53 mutation status will better predict treatment resistance in glioblastoma. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Keywords: CSF1R; PDL1; TP53 isoform; glioblastoma; mutant TP53; tumor-associated macrophages; Δ133p53β.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Antineoplastic Agents, Alkylating / pharmacology
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Line
  • Chemokine CCL2 / metabolism
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / drug therapy
  • Glioblastoma / genetics
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Humans
  • Macrophages / metabolism
  • Mice
  • Mutation
  • Oxidative Stress
  • Protein Isoforms
  • Receptors, Cell Surface / metabolism
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Signal Transduction
  • Temozolomide / pharmacology
  • Tumor Hypoxia
  • Tumor Microenvironment
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation


  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antineoplastic Agents, Alkylating
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CCL2 protein, human
  • CD163 antigen
  • CD274 protein, human
  • CSF1R protein, human
  • Chemokine CCL2
  • Protein Isoforms
  • Receptors, Cell Surface
  • Receptors, Granulocyte-Macrophage Colony-Stimulating Factor
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Temozolomide