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

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 mu...

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Autores principales: Alban, Tyler J., Grabowski, Matthew M., Otvos, Balint, Bayik, Defne, Wang, Wesley, Zalavadia, Ajay, Makarov, Vlad, Troike, Katie, McGraw, Mary, Rabljenovic, Anja, Lauko, Adam, Neumann, Chase, Roversi, Gustavo, Waite, Kristin A., Cioffi, Gino, Patil, Nirav, Tran, Thuy T., McCortney, Kathleen, Steffens, Alicia, Diaz, C. Marcela, Brown, J. Mark, Egan, Kathleen M., Horbinski, Craig M., Barnholtz-Sloan, Jill S., Rajappa, Prajwal, Vogelbaum, Michael A., Bucala, Richard, Chan, Timothy A., Ahluwalia, Manmeet S., Lathia, Justin D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371339/
https://www.ncbi.nlm.nih.gov/pubmed/37252795
http://dx.doi.org/10.1172/jci.insight.160024
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author Alban, Tyler J.
Grabowski, Matthew M.
Otvos, Balint
Bayik, Defne
Wang, Wesley
Zalavadia, Ajay
Makarov, Vlad
Troike, Katie
McGraw, Mary
Rabljenovic, Anja
Lauko, Adam
Neumann, Chase
Roversi, Gustavo
Waite, Kristin A.
Cioffi, Gino
Patil, Nirav
Tran, Thuy T.
McCortney, Kathleen
Steffens, Alicia
Diaz, C. Marcela
Brown, J. Mark
Egan, Kathleen M.
Horbinski, Craig M.
Barnholtz-Sloan, Jill S.
Rajappa, Prajwal
Vogelbaum, Michael A.
Bucala, Richard
Chan, Timothy A.
Ahluwalia, Manmeet S.
Lathia, Justin D.
author_facet Alban, Tyler J.
Grabowski, Matthew M.
Otvos, Balint
Bayik, Defne
Wang, Wesley
Zalavadia, Ajay
Makarov, Vlad
Troike, Katie
McGraw, Mary
Rabljenovic, Anja
Lauko, Adam
Neumann, Chase
Roversi, Gustavo
Waite, Kristin A.
Cioffi, Gino
Patil, Nirav
Tran, Thuy T.
McCortney, Kathleen
Steffens, Alicia
Diaz, C. Marcela
Brown, J. Mark
Egan, Kathleen M.
Horbinski, Craig M.
Barnholtz-Sloan, Jill S.
Rajappa, Prajwal
Vogelbaum, Michael A.
Bucala, Richard
Chan, Timothy A.
Ahluwalia, Manmeet S.
Lathia, Justin D.
author_sort Alban, Tyler J.
collection PubMed
description 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.
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spelling pubmed-103713392023-07-27 The MIF promoter SNP rs755622 is associated with immune activation in glioblastoma Alban, Tyler J. Grabowski, Matthew M. Otvos, Balint Bayik, Defne Wang, Wesley Zalavadia, Ajay Makarov, Vlad Troike, Katie McGraw, Mary Rabljenovic, Anja Lauko, Adam Neumann, Chase Roversi, Gustavo Waite, Kristin A. Cioffi, Gino Patil, Nirav Tran, Thuy T. McCortney, Kathleen Steffens, Alicia Diaz, C. Marcela Brown, J. Mark Egan, Kathleen M. Horbinski, Craig M. Barnholtz-Sloan, Jill S. Rajappa, Prajwal Vogelbaum, Michael A. Bucala, Richard Chan, Timothy A. Ahluwalia, Manmeet S. Lathia, Justin D. JCI Insight Research Article 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. American Society for Clinical Investigation 2023-07-10 /pmc/articles/PMC10371339/ /pubmed/37252795 http://dx.doi.org/10.1172/jci.insight.160024 Text en © 2023 Alban et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Alban, Tyler J.
Grabowski, Matthew M.
Otvos, Balint
Bayik, Defne
Wang, Wesley
Zalavadia, Ajay
Makarov, Vlad
Troike, Katie
McGraw, Mary
Rabljenovic, Anja
Lauko, Adam
Neumann, Chase
Roversi, Gustavo
Waite, Kristin A.
Cioffi, Gino
Patil, Nirav
Tran, Thuy T.
McCortney, Kathleen
Steffens, Alicia
Diaz, C. Marcela
Brown, J. Mark
Egan, Kathleen M.
Horbinski, Craig M.
Barnholtz-Sloan, Jill S.
Rajappa, Prajwal
Vogelbaum, Michael A.
Bucala, Richard
Chan, Timothy A.
Ahluwalia, Manmeet S.
Lathia, Justin D.
The MIF promoter SNP rs755622 is associated with immune activation in glioblastoma
title The MIF promoter SNP rs755622 is associated with immune activation in glioblastoma
title_full The MIF promoter SNP rs755622 is associated with immune activation in glioblastoma
title_fullStr The MIF promoter SNP rs755622 is associated with immune activation in glioblastoma
title_full_unstemmed The MIF promoter SNP rs755622 is associated with immune activation in glioblastoma
title_short The MIF promoter SNP rs755622 is associated with immune activation in glioblastoma
title_sort mif promoter snp rs755622 is associated with immune activation in glioblastoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371339/
https://www.ncbi.nlm.nih.gov/pubmed/37252795
http://dx.doi.org/10.1172/jci.insight.160024
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