The neuroblastoma anti-tumor immune response: macrophage modulation by amyloid precursor-like protein 2

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B106
Abstract ID: 4351

Presenting Author:
Gabrielle L Brumfield , Graduate Research Assistant at Univ. of Nebraska Med. Ctr., Buffett Cancer Ctr., Nebraska Med.

Abstract:

Neuroblastoma (NB), a cancer of immature nerve cells, causes ~15% of pediatric cancer-associated deaths. High infiltration of anti-inflammatory macrophages is observed in advanced NB, creating need for evaluation of phenotypic influences on these intratumoral macrophages. My findings associate anti-inflammatory macrophages with higher expression of amyloid precursor-like protein 2 (APLP2) relative to pro-inflammatory macrophages. In tumors, my lab has shown APLP2 enhances cancer cell migration and reduces surface major histocompatibility complex (MHC) class I. These phenotypes (i.e., increased migration and lowered surface MHC) are also characteristic of anti-inflammatory macrophages. The central hypothesis of this study is that APLP2 promotes anti-inflammatory immunosuppression in NB tumors by affecting macrophage reactivity. Flow cytometry and western blot assessed APLP2 expression and phenotypic shift post stimulus (NB cell-conditioned media, cytokines, PMA) in U937 cells and primary macrophages from wild type and APLP2-knock out mice. Macrophage treatment with NB-conditioned media induced an anti-inflammatory phenotype. Anti-inflammatory macrophages had increased APLP2 expression compared to pro-inflammatory macrophages, and upregulated APLP2 was observed in a model of monocyte-to-macrophage transition. We anticipate identifying the role of APLP2 in NB-reactive macrophages will contribute to future understanding of macrophage physiology and therapeutic development for NB.