Abstract
Exosomes (EXs), a type of extracellular vesicles secreted from various cells and especially cancer cells, mesenchymal cells, macrophages and other cells in the tumor microenvironment (TME), are involved in biologically malignant behaviors of cancers. Recent studies have revealed that EXs contain microRNAs on their inside and express proteins and glycolipids on their outsides, every component of which plays a role in the transmission of genetic and/or epigenetic information in cell-to-cell communications. It is also known that miRNAs are involved in the signal transduction. Thus, EXs may be useful for monitoring the TME of tumor tissues and the invasion and metastasis, processes that are associated with patient survival. Because several solid tumors secrete immune checkpoint proteins, including programmed cell death-ligand 1, the EX-mediated mechanisms are suggested to be potent targets for monitoring patients. Therefore, a companion therapeutic approach against cancer metastasis to distant organs is proposed when surgical removal of the primary tumor is performed. However, EXs and immune checkpoint mechanisms in pancreatic cancer are not fully understood, we provide an update on the recent advances in this field and evidence that EXs will be useful for maximizing patient benefit in precision medicine.
Highlights
Pancreatic cancer is classified as a type of intractable, therapy-resistant cancer, and its overall five-year survival rate has not much changed over the past few decades
The recent study indicated that the pancreatic cancer microbiome can promote oncogenesis by induction of innate and adaptive immune suppression, and bacterial ablation was associated with immunogenic reprogramming in pancreatic tumor microenvironment (TME), with a reduction in myeloid-derived suppressor cells and an increase in M1 macrophage differentiation, leading to an efficacy for checkpoint-targeted immunotherapy by upregulating PD-1 expression [67]
extracellular vesicles (EVs) are as expected from the nature of EVs, the recent study indicates that EVs or EV-like nanovesicles will be useful for the potential therapeutic usage as a prospective immunosuppressant, and proposed the possible usage of dual-targeting vesicles, composed of programmed cell death-ligand 1/programmed cell death 1 (PD-L1/PD-1) and cytotoxic T-lymphocyte-associated protein 4/cluster of differentiation 80 (CTLA-4/CD80) [79]
Summary
Pancreatic cancer is classified as a type of intractable, therapy-resistant cancer, and its overall five-year survival rate has not much changed over the past few decades. Pancreatic cancer is predicted to be the second-leading cause of cancer-related mortality in the decade in Western countries [1]. Pancreatic cancer is reported to cause tissue invasion and metastasis to distant organs in the early stage of carcinogenesis and during clinical diagnosis, tumors are typically already in the advanced stages [2]. Several research efforts have focused on the effectiveness of immune therapy combined with surgery, evidence for its use in controlling pancreatic cancer is not enough [3]. We update and focus on the recent advances in the field of immuno-surgical therapeutic strategy for pancreatic cancer, which was emerged recently in the relevant of extracellular vesicles (EVs) such as exosomes (EXs) [4]
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