Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Dec;17(3-4):381-397.
doi: 10.1007/s11481-021-10018-3. Epub 2021 Oct 25.

Can Soluble Immune Checkpoint Molecules on Exosomes Mediate Inflammation?

Julie Joseph  1 , Benjamin Rahmani  1 , Yonesha Cole  1 , Neha Puttagunta  1 , Edward Lin  1 , Zafar K Khan  1 , Pooja Jain  2   3
Affiliations
Review

Can Soluble Immune Checkpoint Molecules on Exosomes Mediate Inflammation?

Julie Joseph et al. J Neuroimmune Pharmacol. 2022 Dec.

Abstract

Immune checkpoints (ICPs) are major co-signaling pathways that trigger effector functions in immune cells, with isoforms that are either membrane bound, engaging in direct cell to cell activation locally, or soluble, acting at distant sites by circulating freely or potentially via extracellular vesicles (EVs). Exosomes are small EVs secreted by a variety of cells carrying various proteins and nucleic acids. They are distributed extensively through biological fluids and have major impacts on infectious diseases, cancer, and neuroinflammation. Similarly, ICPs play key roles in a variety of disease conditions and have been extensively utilized as a prognostic tool for various cancers. Herein, we explored if the association between exosomes and ICPs could be a significant contributor of inflammation, particularly in the setting of cancer, neuroinflammation and viral infections, wherein the up regulation in both exosomal proteins and ICPs correlate with immunosuppressive effects. The detailed literature review of existing data highlights the significance and complexity of these two important pathways in mediating cancer and potentiating neuroinflammation via modulating overall immune response. Cells increasingly secret exosomes in response to intracellular signals from invading pathogens or cancerous transformations. These exosomes can carry a variety of cargo including proteins, nucleic acids, cytokines, and receptors/ligands that have functional consequences on recipient cells. Illustration generated using BioRender software.

Keywords: Cancer; Exosome; Immune checkpoints; Neuroinflammation; Viral infections.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest The authors declare that the research for this manuscript was conducted in the absence of any financial or commercial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
Generation of soluble and membranous ICPs. DNA encoding an immune checkpoint receptor/ligand is transcribed into mRNA in the nucleus and is alternatively spliced, leading to soluble or membrane bound isoforms. The respective mRNAs are translated in the ER and further modified in the Golgi. The membrane bound isoforms are transported from the Golgi and fuse into the plasma membrane while the soluble isoforms can be released directly into the extracellular environment (ECM) or as cargo within or bound to an exosome. Figures were generated using BioRender software
Fig. 2
Fig. 2
Overview of exosome biogenesis. Endosomes enters the cell either by invagination or receptor mediated endocytosis. Through a sequence of intraluminal invagination and endosomal sorting, the endosome transforms into multivesicular bodies (MVB) and then matures into a late endosome. During this phase, the contents that are ultimately secreted in the exosome are added through modifications and transport complexes within the MVB, the ER and Golgi. MVBs, are then either transported to the plasma membrane and fuse with the plasma membrane or directed to lysosomes where their content is degraded (not shown). Ultimately, exosomal content is a heterogeneous mixture of cargo inside and on the surface, depending on the parent cell, including host proteins- cell specific or ubiquitous, nucleic acids, ICPs, lipids, pathogen associated molecules and other metabolites. Figures were generated using BioRender software
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abbar B et al. (2020) Immune checkpoint inhibitors in people living with HIV: what about anti-HIV effects? AIDS 34(2):167. - PubMed
    1. Abusamra AJ et al. (2005) Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis. Blood Cells Mol Dis 35(2):169–173 - PubMed
    1. Acharya N, Sabatos-Peyton C, Anderson AC (2020) Tim-3 finds its place in the cancer immunotherapy landscape. J Immunother Cancer 8(1):e000911. - PMC - PubMed
    1. Adashek JJ et al. (2019) Remembering the forgotten child: the role of immune checkpoint inhibition in patients with human immunod eficiency virus and cancer. J Immunother Cancer 7(1):130. - PMC - PubMed
    1. Alenquer M, Amorim MJ (2015) Exosome biogenesis, regulation, and function in viral infection. Viruses 7(9):5066–5083 - PMC - PubMed

Publication types

Substances

LinkOut - more resources