Open AccessDendritic cells loaded with exosomes derived from cancer stem cell‐enriched spheroids as a potential immunotherapeutic option
Author(s) -
Naseri Marzieh,
Zöller Margot,
Hadjati Jamshid,
Ghods Roya,
Ranaei Pirmardan Ehsan,
Kiani Jafar,
Eini Leila,
Bozorgmehr Mahmood,
Madjd Zahra
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16401
Subject(s) - microvesicles , antigen , cancer research , immunotherapy , cancer stem cell , cancer immunotherapy , dendritic cell , cell , chemistry , exosome , stem cell , immune system , biology , immunology , microbiology and biotechnology , microrna , biochemistry , gene
Cancer stem cells (CSCs) are responsible for therapeutic resistance and recurrence in colorectal cancer. Despite advances in immunotherapy, the inability to specifically eradicate CSCs has led to treatment failure. Hence, identification of appropriate antigen sources is a major challenge in designing dendritic cell (DC)‐based therapeutic strategies against CSCs. Here, in an in vitro model using the HT‐29 colon cancer cell line, we explored the efficacy of DCs loaded with exosomes derived from CSC‐enriched colonospheres (CSC enr ‐EXOs) as an antigen source in activating CSC‐specific T‐cell responses. HT‐29 lysate, HT‐29‐EXOs and CSC enr lysate were independently assessed as separate antigen sources. Having confirmed CSCs enrichment in spheroids, CSC enr ‐EXOs were purified and characterized, and their impact on DC maturation was investigated. Finally, the impact of the antigen‐pulsed DCs on the proliferation rate and also spheroid destructive capacity of autologous T cells was assessed. CSC enr ‐EXOs similar to other antigen groups had no suppressive/negative impacts on phenotypic maturation of DCs as judged by the expression level of costimulatory molecules. Notably, similar to CSC enr lysate, CSC enr ‐EXOs significantly increased the IL‐12/IL‐10 ratio in supernatants of mature DCs. CSC enr ‐EXO‐loaded DCs effectively promoted T‐cell proliferation. Importantly, T cells stimulated with CSC enr ‐EXOs disrupted spheroids' structure. Thus, CSC enr ‐EXOs present a novel and promising antigen source that in combination with conventional tumour bulk‐derived antigens should be further explored in pre‐clinical immunotherapeutic settings for the efficacy in hampering recurrence and metastatic spread.