Year: 2022
Type: preprint
Study design: Observational Study
Abstract: While immunotherapies have shown durable responses for multiple tumors, their efficacy remains limited in some advanced cancers, including glioblastoma. This may be due to differences in the immune landscape, as the glioblastoma microenvironment strongly favors immunosuppressive myeloid cells, which are linked to an elevation in immune-suppressive cytokines, including macrophage migration inhibitory factor (MIF). We now find that a single-nucleotide polymorphism (SNP) rs755622 in the MIF promoter associates with increased leukocyte infiltration in glioblastoma. Furthermore, we identified lactotransferrin expression as being associated with the rs755622 SNP, which could also be used as a biomarker for immune infiltrated tumors. These findings provide the first example in glioblastoma of a germline SNP that underlies differences in the immune microenvironment and identifies high lactotransferrin as a potential factor promoting immune activation.
Authors: Tyler J. Alban, Matthew M. Grabowski, Balint Otvos, Defne Bayik, 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, Michael A. Vogelbaum, Richard Bucala, Timothy A. Chan, Manmeet S. Ahluwalia, Justin D. Lathia
Institutions: Cleveland Clinic, Cleveland Clinic Research, National Cancer Institute, Division of Cancer Epidemiology and Genetics, University Hospitals of Cleveland, Yale Cancer Center, 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: green
Award: G180317997
OpenAlex ID: W4221118466