T Lymphocyte and CAR-T Cell-Derived Extracellular Vesicles and Their Applications in Cancer Therapy

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 Mar 10

PMID 35269412

Authors

Victor Calvo

Manuel Izquierdo

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles (EV) are a very diverse group of cell-derived vesicles released by almost all kind of living cells. EV are involved in intercellular exchange, both nearby and systemically, since they induce signals and transmit their cargo (proteins, lipids, miRNAs) to other cells, which subsequently trigger a wide variety of biological responses in the target cells. However, cell surface receptor-induced EV release is limited to cells from the immune system, including T lymphocytes. T cell receptor activation of T lymphocytes induces secretion of EV containing T cell receptors for antigen and several bioactive molecules, including proapoptotic proteins. These EV are specific for antigen-bearing cells, which make them ideal candidates for a cell-free, EV-dependent cancer therapy. In this review we examine the generation of EV by T lymphocytes and CAR-T cells and some potential therapeutic approaches of these EV.

Citing Articles

The multifaceted roles of extracellular vesicles for therapeutic intervention with non-Hodgkin lymphoma.

Lee A, Godwin A, Abdelhakim H Extracell Vesicles Circ Nucl Acids. 2024; 5(2):329-343.

PMID: 39639879 PMC: 11618822. DOI: 10.20517/evcna.2024.07.

Exosomal circular RNAs in tumor microenvironment: An emphasis on signaling pathways and clinical opportunities.

Li J, Zhou W, Wang H, Huang M, Deng H MedComm (2020). 2024; 5(12):e70019.

PMID: 39584047 PMC: 11586091. DOI: 10.1002/mco2.70019.

Focusing on exosomes to overcome the existing bottlenecks of CAR-T cell therapy.

Zhang S, Peng L, Chen Y, Xu Y, Moradi V Inflamm Regen. 2024; 44(1):45.

PMID: 39490997 PMC: 11533312. DOI: 10.1186/s41232-024-00358-x.

Exploring the potential of the convergence between extracellular vesicles and CAR technology as a novel immunotherapy approach.

Bar O, Porgador A, Cooks T J Extracell Biol. 2024; 3(9):e70011.

PMID: 39328262 PMC: 11424882. DOI: 10.1002/jex2.70011.

Extracellular vesicles and cancer stem cells: a deadly duo in tumor progression.

Tayanloo-Beik A, Eslami A, Sarvari M, Jalaeikhoo H, Rajaeinejad M, Nikandish M Oncol Rev. 2024; 18:1411736.

PMID: 39091989 PMC: 11291337. DOI: 10.3389/or.2024.1411736.

References

Alonso R, Mazzeo C, Rodriguez M, Marsh M, Fraile-Ramos A, Calvo V . Diacylglycerol kinase α regulates the formation and polarisation of mature multivesicular bodies involved in the secretion of Fas ligand-containing exosomes in T lymphocytes. Cell Death Differ. 2011; 18(7):1161-73. PMC: 3131963. DOI: 10.1038/cdd.2010.184. View

Ruella M, Xu J, Barrett D, Fraietta J, Reich T, Ambrose D . Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell. Nat Med. 2018; 24(10):1499-1503. PMC: 6511988. DOI: 10.1038/s41591-018-0201-9. View

Scott C, Vacca F, Gruenberg J . Endosome maturation, transport and functions. Semin Cell Dev Biol. 2014; 31:2-10. DOI: 10.1016/j.semcdb.2014.03.034. View

Choudhuri K, Llodra J, Roth E, Tsai J, Gordo S, Wucherpfennig K . Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse. Nature. 2014; 507(7490):118-23. PMC: 3949170. DOI: 10.1038/nature12951. View

Billadeau D, Nolz J, Gomez T . Regulation of T-cell activation by the cytoskeleton. Nat Rev Immunol. 2007; 7(2):131-43. DOI: 10.1038/nri2021. View

Vogel R, Savage J, Muzard J, Della Camera G, Vella G, Law A . Measuring particle concentration of multimodal synthetic reference materials and extracellular vesicles with orthogonal techniques: Who is up to the challenge?. J Extracell Vesicles. 2021; 10(3):e12052. PMC: 7804049. DOI: 10.1002/jev2.12052. View

Geuze H . The role of endosomes and lysosomes in MHC class II functioning. Immunol Today. 1998; 19(6):282-7. DOI: 10.1016/s0167-5699(98)01269-9. View

Feldmann J, Callebaut I, Raposo G, Certain S, Bacq D, Dumont C . Munc13-4 is essential for cytolytic granules fusion and is mutated in a form of familial hemophagocytic lymphohistiocytosis (FHL3). Cell. 2003; 115(4):461-73. DOI: 10.1016/s0092-8674(03)00855-9. View

Obino D, Farina F, Malbec O, Saez P, Maurin M, Gaillard J . Actin nucleation at the centrosome controls lymphocyte polarity. Nat Commun. 2016; 7:10969. PMC: 4802043. DOI: 10.1038/ncomms10969. View

10.

Quann E, Merino E, Furuta T, Huse M . Localized diacylglycerol drives the polarization of the microtubule-organizing center in T cells. Nat Immunol. 2009; 10(6):627-35. DOI: 10.1038/ni.1734. View

11.

Robbins P, Morelli A . Regulation of immune responses by extracellular vesicles. Nat Rev Immunol. 2014; 14(3):195-208. PMC: 4350779. DOI: 10.1038/nri3622. View

12.

Huse M, Quann E, Davis M . Shouts, whispers and the kiss of death: directional secretion in T cells. Nat Immunol. 2008; 9(10):1105-11. PMC: 2905669. DOI: 10.1038/ni.f.215. View

13.

Thery C, Zitvogel L, Amigorena S . Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002; 2(8):569-79. DOI: 10.1038/nri855. View

14.

Peters P, Borst J, Oorschot V, Fukuda M, Krahenbuhl O, Tschopp J . Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes. J Exp Med. 1991; 173(5):1099-109. PMC: 2118839. DOI: 10.1084/jem.173.5.1099. View

15.

Sterner R, Sterner R . CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J. 2021; 11(4):69. PMC: 8024391. DOI: 10.1038/s41408-021-00459-7. View

16.

van der Vlist E, Arkesteijn G, van de Lest C, Stoorvogel W, Nolte-t Hoen E, Wauben M . CD4(+) T cell activation promotes the differential release of distinct populations of nanosized vesicles. J Extracell Vesicles. 2013; 1. PMC: 3760647. DOI: 10.3402/jev.v1i0.18364. View

17.

Sanchez E, Liu X, Huse M . Actin clearance promotes polarized dynein accumulation at the immunological synapse. PLoS One. 2019; 14(7):e0210377. PMC: 6608937. DOI: 10.1371/journal.pone.0210377. View

18.

Bello-Gamboa A, Velasco M, Moreno S, Herranz G, Ilie R, Huetos S . Actin reorganization at the centrosomal area and the immune synapse regulates polarized secretory traffic of multivesicular bodies in T lymphocytes. J Extracell Vesicles. 2020; 9(1):1759926. PMC: 7480611. DOI: 10.1080/20013078.2020.1759926. View

19.

Fernandez L, Metais J, Escudero A, Vela M, Valentin J, Vallcorba I . Memory T Cells Expressing an NKG2D-CAR Efficiently Target Osteosarcoma Cells. Clin Cancer Res. 2017; 23(19):5824-5835. DOI: 10.1158/1078-0432.CCR-17-0075. View

20.

van Niel G, Porto-Carreiro I, Simoes S, Raposo G . Exosomes: a common pathway for a specialized function. J Biochem. 2006; 140(1):13-21. DOI: 10.1093/jb/mvj128. View