Exosomes Derived from Endoplasmic Reticulum Stressed Hepatocellular Carcinoma Cells Enhance the Antitumor Immunity of Dendritic Cells

Overview

Journal Inflammation

Specialties Allergy & Immunology
Pathology

Date 2024 Dec 23

PMID 39714721

Authors

Ju Zhang

Jiatao Liu

Jing Ni

Xiao Lin

Lulu Fan

Guoping Sun

Affiliations

Soon will be listed here.

Abstract

Endoplasmic reticulum stress (ERs) is implicated in antitumor immunity. However, the exact role of ERs in mediating the effects of dendritic cells (DCs) is not unclear. In this study, we explored the role of exosomes derived from ER-stressed hepatocellular carcinoma (HCC) cells in the antitumor effects of DCs and the precise underlying mechanism. We found that ER-stressed HCC cells secreted more exosomes (EXO-TM) than those without ER stress (EXO-CON) and that exosomes were effectively taken up by DCs. EXO-TM significantly promoted DCs maturation, as demonstrated by the increased expression of HLA-ABC, CD83, CD80, CD86, and pro-inflammatory cytokines and the decreased expression of IL-10. Moreover, EXO-TM pulsed DCs (DC) significantly enhanced T lymphocyte-mediated lysis against several types of tumor cells by promoting the proliferation of CD3CD8 T cells and increasing the expression of INF-γ both in vitro and in vivo. Mechanistically, we found that heat shock protein (HSP) 90 was more significantly enriched in EXO-TM than in EXO-CON cells, and the knockdown of HSP90 remarkably reversed EXO-TM-mediated DC activation. Our results suggest that exosomes derived from ER-stressed HCC cells could enhance the antitumor effect of DC-mediated T lymphocytes, which may be related to the large amount of HSP90 carried in the exosomes. Therefore, regulating the HSP90 carrying capacity of tumor exosomes may be an effective immunotherapy strategy.

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