The MIF promoter SNP rs755622 is associated with immune activation in glioblastoma

JCI Insight. 2023 Jul 10;8(13):e160024. doi: 10.1172/jci.insight.160024.

Abstract

Intratumoral heterogeneity is a defining hallmark of glioblastoma, driving drug resistance and ultimately recurrence. Many somatic drivers of microenvironmental change have been shown to affect this heterogeneity and, ultimately, the treatment response. However, little is known about how germline mutations affect the tumoral microenvironment. Here, we find that the single-nucleotide polymorphism (SNP) rs755622 in the promoter of the cytokine macrophage migration inhibitory factor (MIF) is associated with increased leukocyte infiltration in glioblastoma. Furthermore, we identified an association between rs755622 and lactotransferrin expression, which could also be used as a biomarker for immune-infiltrated tumors. These findings demonstrate that a germline SNP in the promoter region of MIF may affect the immune microenvironment and further reveal a link between lactotransferrin and immune activation.

Keywords: Brain cancer; Cellular immune response; Immunology; Immunotherapy; Oncology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glioblastoma* / genetics
  • Humans
  • Intramolecular Oxidoreductases / genetics
  • Lactoferrin / genetics
  • Macrophage Migration-Inhibitory Factors* / genetics
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Tumor Microenvironment / genetics

Substances

  • Lactoferrin
  • Macrophage Migration-Inhibitory Factors
  • MIF protein, human
  • Intramolecular Oxidoreductases