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Intratumoral administration of the antisecretory peptide AF16 cures murine gliomas and modulates macrophage functions

Kopecky, Jan LU orcid ; Pérez, Julio Enríquez LU orcid ; Eriksson, Håkan ; Visse, Edward LU ; Siesjö, Peter LU orcid and Darabi, Anna LU (2022) In Scientific Reports 12.
Abstract

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... (More)

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.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
12
article number
4609
publisher
Nature Publishing Group
external identifiers
  • pmid:35301393
  • scopus:85126536923
ISSN
2045-2322
DOI
10.1038/s41598-022-08618-x
language
English
LU publication?
yes
id
34a1f2fb-f93a-4dee-af3d-869a1c77fb10
date added to LUP
2022-05-20 16:21:23
date last changed
2025-03-22 21:37:01
@article{34a1f2fb-f93a-4dee-af3d-869a1c77fb10,
  abstract     = {{<p>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.</p>}},
  author       = {{Kopecky, Jan and Pérez, Julio Enríquez and Eriksson, Håkan and Visse, Edward and Siesjö, Peter and Darabi, Anna}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Intratumoral administration of the antisecretory peptide AF16 cures murine gliomas and modulates macrophage functions}},
  url          = {{http://dx.doi.org/10.1038/s41598-022-08618-x}},
  doi          = {{10.1038/s41598-022-08618-x}},
  volume       = {{12}},
  year         = {{2022}},
}