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Intratumoral administration of the antisecretory peptide AF16 cures murine gliomas and modulates macrophage functions
Lund Univ, Fac Med, Dept Clin Sci Lund, Glioma Immunotherapy Grp,Div Neurosurg, Barngatan 4, S-22185 Lund, Sweden..
Lund Univ, Fac Med, Dept Clin Sci Lund, Glioma Immunotherapy Grp,Div Neurosurg, Barngatan 4, S-22185 Lund, Sweden..
Malmö University, Faculty of Health and Society (HS), Department of Biomedical Science (BMV).ORCID iD: 0000-0003-0769-9988
Lund Univ, Fac Med, Dept Clin Sci Lund, Glioma Immunotherapy Grp,Div Neurosurg, Barngatan 4, S-22185 Lund, Sweden..
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2022 (English)In: Scientific Reports, E-ISSN 2045-2322, Vol. 12, no 1, article id 4609Article in journal (Refereed) Published
Abstract [en]

Glioblastoma has remained the deadliest primary brain tumor while its current therapy offers only modest survival prolongation. Immunotherapy has failed to record notable benefits in routine glioblastoma treatment. Conventionally, immunotherapy relies on T cells as tumor-killing agents; however, T cells are outnumbered by macrophages in glioblastoma microenvironment. In this study, we explore the effect of AF16, a peptide from the endogenous antisecretory factor protein, on the survival of glioma-bearing mice, the tumor size, and characteristics of the tumor microenvironment with specific focus on macrophages. We elucidate the effect of AF16 on the inflammation-related secretome of human and murine macrophages, as well as human glioblastoma cells. In our results, AF16 alone and in combination with temozolomide leads to cure in immunocompetent mice with orthotopic GL261 gliomas, as well as prolonged survival in immunocompromised mice. We recorded decreased tumor size and changes in infiltration of macrophages and T cells in the murine glioma microenvironment. Human and murine macrophages increased expression of proinflammatory markers in response to AF16 treatment and the same effect was seen in human primary glioblastoma cells. In summary, we present AF16 as an immunomodulatory factor stimulating pro-inflammatory macrophages with a potential to be implemented in glioblastoma treatment protocols.

Place, publisher, year, edition, pages
Nature Publishing Group, 2022. Vol. 12, no 1, article id 4609
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Cancer and Oncology
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URN: urn:nbn:se:mau:diva-50907DOI: 10.1038/s41598-022-08618-xISI: 000770396200055PubMedID: 35301393Scopus ID: 2-s2.0-85126536923OAI: oai:DiVA.org:mau-50907DiVA, id: diva2:1649217
Available from: 2022-04-04 Created: 2022-04-04 Last updated: 2024-02-05Bibliographically approved

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Eriksson, Håkan

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