The MIF SNP rs755622 is a germline determinant of tumor immune activation in Glioblastoma

Alban, T.; Grabowski, M. M.; Otvos, B.; Watson, D. B.; Zalavadia, A.; Makarav, V.; Troike, K. M.; McGraw, M.; Rabljenovic, A.; Lauko, A.; Neumann, C. K. A.; Roversi, G.; Waite, K.; Cioffi, G.; Patil, N.; Tran, T.; McCortney, K.; Steffens, A.; Diaz, M.; Brown, J. M.; Egan, K.; Horbinski, C.; Barnholtz-sloan, J.; Vogelbaum, M.; Bucala, R.; Chan, T.; Ahluwalia, M.; Lathia, J.

doi:10.1101/2022.03.07.483365

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bioRxiv · 10.1101/2022.03.07.483365

The MIF SNP rs755622 is a germline determinant of tumor immune activation in Glioblastoma

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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.

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Alban, T., Grabowski, M. M., Otvos, B., Watson, D. B., Zalavadia, A., Makarav, V., Troike, K. M., McGraw, M., Rabljenovic, A., Lauko, A., Neumann, C. K. A., Roversi, G., Waite, K., Cioffi, G., Patil, N., Tran, T., McCortney, K., Steffens, A., Diaz, M., Brown, J. M., Egan, K., Horbinski, C., Barnholtz-sloan, J., Vogelbaum, M., Bucala, R., Chan, T., Ahluwalia, M., Lathia, J.. 2022-03-08. The MIF SNP rs755622 is a germline determinant of tumor immune activation in Glioblastoma. https://doi.org/10.1101/2022.03.07.483365

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