| Title: |
Enriched Environment Cues Suggest a New Strategy to Counteract Glioma: Engineered rAAV2-IL-15 Microglia Modulate the Tumor Microenvironment |
| Authors: |
Alessandro Mormino; Giovanni Bernardini; Germana Cocozza; Nicoletta Corbi; Claudio Passananti; Angela Santoni; Cristina Limatola; Stefano Garofalo |
| Contributors: |
Mormino, Alessandro; Bernardini, Giovanni; Cocozza, Germana; Corbi, Nicoletta; Passananti, Claudio; Santoni, Angela; Limatola, Cristina; Garofalo, Stefano |
| Publication Year: |
2021 |
| Collection: |
Sapienza Università di Roma: CINECA IRIS |
| Subject Terms: |
Microglia; interleukin-15; enriched environment |
| Description: |
Several types of cancer grow differently depending on the environmental stimuli they receive. In glioma, exposure to an enriched environment (EE) increases the overall survival rate of tumor-bearing mice, acting on the cells that participate to define the tumor microenvironment. In particular, environmental cues increase the microglial production of interleukin (IL)-15 which promotes a pro-inflammatory (antitumor) phenotype of microglia and the cytotoxic activity of natural killer (NK) cells, counteracting glioma growth, thus representing a virtuous mechanism of interaction between NK cells and microglia. To mimic the effect of EE on glioma, we investigated the potential of creating engineered microglia as the source of IL-15 in glioma. We demonstrated that microglia modified with recombinant adeno-associated virus serotype 2 (rAAV2) carrying IL-15 (rAAV2-IL-15), to force the production of IL-15, are able to increase the NK cells viability in coculture. Furthermore, the intranasal delivery of rAAV2-IL-15 microglia triggered the interplay with NK cells in vivo, enhancing NK cell recruitment and pro-inflammatory microglial phenotype in tumor mass of glioma-bearing mice, and ultimately counteracted tumor growth. This approach has a high potential for clinical translatability, highlighting the therapeutic efficacy of forced IL-15 production in microglia: the delivery of engineered rAAV2-IL-15 microglia to boost the immune response paves the way to design a new perspective therapy for glioma patients. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/wos/WOS:000717469100001; journal:FRONTIERS IN IMMUNOLOGY; http://hdl.handle.net/11573/1571567 |
| DOI: |
10.3389/fimmu.2021.730128 |
| Availability: |
http://hdl.handle.net/11573/1571567; https://doi.org/10.3389/fimmu.2021.730128 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.56281928 |
| Database: |
BASE |