Intratumoral Administration Immunogenic Exosomes can Modify Tumor Immune Microenvironment

Author:

Kalami Arman1,Poursalehi Zahra2,Gharalari Farzaneh Hosseini2,Molavi Hana1,Tollabi Mohammad3,Nasiri-Motlagh Behnam4,Shahgolzari Mehdi1,Khosroshahi Ahmad Yari1

Affiliation:

1. Tabriz University of Medical Sciences

2. Urmia University of Medical Sciences

3. Iran University of Medical Sciences

4. Shahid Madani Hospital

Abstract

Abstract It has been observed that external stress or stimuli can initiate apoptosis and produce extracellular vesicles known as exosomes. Recent studies suggest that exosomes can trigger an anti-tumor immune response. In the current study, exosomes secreted by the 4T1 triple-negative breast cancer (TNBC) cell line under stress conditions (Dox, X-ray irradiation, and cold plasma treatments) were studied. The stress-induced exosomes were harvested, differing in their ability to present some DAMP proteins such as HSP70 and HMGB1. These exosomes can enhance the expression of pro-inflammatory molecules by immune cells at different levels in different treatments. Additionally, intratumoral administration of these exosomes has been shown to modify the tumor immune microenvironment (TIME) in a TNBC murine model differently. We have concluded that exosomes secreted by the 4T1 cell line under Dox treatment can significantly reduce tumor volume and modify the tumor microenvironment. However, other treatment methods produce immunogenic exosomes that are neither effective nor appropriate. Nevertheless, many studies report that these methods have significant therapeutic effects when used directly.

Publisher

Research Square Platform LLC

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