Abstract
Cancer stem cells (CSCs), which have the capacity to self-renew and differentiate into various types of cells, are notorious for their roles in tumor initiation, metastasis, and therapy resistance. Thus, underlying mechanisms for their survival provide key insights into developing effective therapeutic strategies. A more recent focus has been on exosomes that play a role in transmitting information between CSCs and non-CSCs, resulting in activating CSCs for cancer progression and modulating their surrounding microenvironment. The field of CSC-derived exosomes (CSCEXs) for different types of cancer is still under exploration. A deeper understanding and further investigation into CSCEXs’ roles in tumorigenicity and the identification of novel exosomal components are necessary for engineering exosomes for the treatment of cancer. Here, we review the features of CSCEXs, including surface markers, cargo, and biological or physiological functions. Further, reports on the immunomodulatory effects of CSCEXs are summarized, and exosome engineering for CSC-targeting is also discussed.
Highlights
Published: 1 May 2021The majority of human cancers display heterogeneity in morphology, expression of cell surface markers, and proliferative or angiogenic potential [1]
A study on breast cancer stem cells showed that released exosomes carry high miR levels associated with metastasis [57], and another study reported that CSC-derived exosomes enhanced cancer cell resistance to chemotherapy, such as doxorubicin and paclitaxel by miR-155 [58]
Both CSC-derived exosomes (CSCEXs) and Tumor-derived exosomes (TEXs) seem to affect tumor progression, the biomarkers/cargos expressed in CSCs contribute to metastasis more than those expressed in non-stem tumor cells do [67]
Summary
The majority of human cancers display heterogeneity in morphology, expression of cell surface markers, and proliferative or angiogenic potential [1]. Intrinsic mechanisms, including acquired mutations and the “cells of origin”, drive a heterogeneous population of tumor cells, and extrinsic factors from the microenvironment influence the fate of the cells [2]. This results in tumor cells with genetically distinct molecular signatures and therapy resistance [3]. A cell-free cancer vaccine candidate using α-fetoprotein-enriched exosomes derived from dendritic cells (DCs) can contribute to adoptive immunotherapy [24] This stimulates the production of interferon-γ and interleukin (IL)-2 and reduces the expression of TGF-β and IL-10 at the tumor site. The features of CSC-associated exosomes, including surface markers, cargo, biological or physiological functions, and immunomodulatory effects, are summarized, and future possibilities for the development of exosome-based cancer immunotherapeutics are discussed
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