The MIF promoter SNP rs755622 is associated with immune activation in glioblastoma
Year: 2023
Type: article
Study design: Observational Study
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.
Source: JCI Insight
Authors: Tyler J. Alban, Matthew M. Grabowski, Balint Otvos, Defne Bayik, Wesley Wang, Ajay Zalavadia, Vlad Makarov, Katie Troike, Mary McGraw, Anja Rabljenovic, Adam Lauko, Chase Neumann, Gustavo Roversi, Kristin A. Waite, Gino Cioffi, Nirav Patil, Thuy T. Tran, Kathleen McCortney, Alicia Steffens, C. Marcela Diaz, J. Mark Brown, Kathleen M. Egan, Craig M. Horbinski, Jill S. Barnholtz-Sloan, Prajwal Rajappa, Michael A. Vogelbaum, Richard Bucala, Timothy A. Chan, Manmeet S. Ahluwalia, Justin D. Lathia
Institutions: Cleveland Clinic, Cleveland Clinic Research, Nationwide Children's Hospital, The Ohio State University Wexner Medical Center, The Ohio State University, National Institutes of Health, National Cancer Institute, Center for Cancer Research, Division of Cancer Epidemiology and Genetics, University Hospitals of Cleveland, Yale Cancer Center, Yale University, Northwestern University, Cleveland Clinic Lerner College of Medicine, Case Comprehensive Cancer Center, Case Western Reserve University, Moffitt Cancer Center, Baptist Hospital of Miami, Baptist Health South Florida
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,100
Funders: AstraZeneca, Cleveland Clinic, Case Comprehensive Cancer Center, Case Western Reserve University, Novocure, Incyte, National Institutes of Health, Pharmacyclics, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences
Awards: G180317997, The immunosuppressive role of glioblastoma-derived macrophage migration inhibitor factor, Medical Scientist Training Program, Role of SerpinB3 in glioblastoma cancer stem cells, Role of myeloid-derived suppressor cells in local and systemic immunosuppression in glioblastoma, Towards Precision Immuno-Oncology: Unraveling the Genomic Determinants and Mechanisms Underlying Immunotherapy Efficacy and Resistance, Deciphering MDSC function for GBM targeting, YALE CANCER CENTER CALABRESI IMMUNO-ONCOLOGY TRAINING PROGRAM, Yale Clinical and Translational Science Award, Cancer Biology Training Grant
OpenAlex ID: W4378782219