Investigation of immunomodulatory properties of anti-secretory factor in experimental brain tumor models

University essay from Lunds universitet/Läkarutbildningen

Abstract: Introduction: Glioblastoma is the most aggressive form of primary brain tumor in adults. Current treatment including chemotherapy poses a limitation due to consequences of systemic toxicity. Further studies for alternative, multimodal treatments are necessary. Antisecretory factor is an endogenous protein. Studies have shown that it has anti-inflammatory and immune modulatory effects in experimental models. The active peptide of antisecretory factor, AF-16, modulates cytokine and chemokine secretion from myeloid and tumor cells in a manner that affects immune suppression, immune cell recruitment and treatment efficacy. Aims: To investigate the immunomodulatory effect of AF-16 in in vitro cell cultures of glioblastoma cells and myeloid immune cells (monocytes and macrophages). To investigate AF-16 mediated treatment efficacy in in vivo glioma mouse models. Methods: Cell cultures (human monocytes, macrophages and glioblastoma cells) treated with different doses of AF-16 were analyzed using different protein platforms (Olink Proteomics, Mesoscale Discovery). 3-day mini-osmotic pumps (Alzet®) were used to deliver AF-16 to tumor bearing mice and survival was assessed between treated and non-treated mice. Immune cell populations in tumors from treated and non-treated mice were analyzed by immunohistochemistry. Results: AF-16 affected the expression of several inflammatory proteins. 2/8 mice survived in the AF-16 treated group compared to 0/8 in the non-treated group. However, the median survival time was equal between groups therefore data was not statistically significant. Immunohistochemical images indicated modest modification in macrophage concentration at the tumor site in treated mice, however no quantitative analysis was performed. Conclusion: AF-16 affects expression of several inflammatory proteins in immune- and glioblastoma cells. AF-16 treatment has the potential to cure animals with brain tumors and modulates the distribution of macrophages at the tumor site. The exact therapeutic benefit and mechanism of action remains to be elucidated but we provide indications that it involves the myeloid branch of the immune system of the host.

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