The potential role of tumor-derived exosomes in diagnosis, prognosis, and response to therapy in cancer

References

• Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017 Jan 18;541(7637):321–330.
   PubMed Web of Science ®Google Scholar
• Beatty GL, Gladney WL. Immune escape mechanisms as a guide for cancer immunotherapy. Clin Cancer Res. 2015 Feb 15;21(4):687–692.
   PubMed Web of Science ®Google Scholar
• Pitt JM, Vetizou M, Daillere R, et al. Resistance mechanisms to immune-checkpoint blockade in cancer: tumor-intrinsic and -extrinsic factors. Immunity. 2016 Jun 21;44(6):1255–1269.
   PubMed Web of Science ®Google Scholar
• Yu P, Lee Y, Liu W, et al. Intratumor depletion of CD4+ cells unmasks tumor immunogenicity leading to the rejection of late-stage tumors. J Exp Med. 2005 Mar 7;201(5):779–791.
   PubMed Web of Science ®Google Scholar
• Garcia-Gomez A, Rodriguez-Ubreva J, Ballestar E. Epigenetic interplay between immune, stromal and cancer cells in the tumor microenvironment. Clin Immunol. 2018 Nov;196:64–71.
   PubMed Web of Science ®Google Scholar
• Shimizu K, Iyoda T, Okada M, et al. Immune suppression and reversal of the suppressive tumor microenvironment. Int Immunol. 2018 Sep 25;30(10):445–454.
   PubMed Web of Science ®Google Scholar
• Whiteside TL. Exosome and mesenchymal stem cell cross-talk in the tumor microenvironment. Semin Immunol. 2018 Feb;35:69–79.
   PubMed Web of Science ®Google Scholar
• Ludwig N, Hong CS, Ludwig S, et al. Isolation and analysis of tumor-derived exosomes. Curr Protoc Immunol. 2019 Dec;127(1):e91.
   PubMedGoogle Scholar
• Thery C, Witwer KW, Aikawa E, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the international society for extracellular vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7(1):1535750.
   PubMed Web of Science ®Google Scholar
• KM M, Kalluri R. Mechanisms associated with biogenesis of exosomes in cancer. Mol Cancer. 2019 Mar 30;18(1):52.
   PubMed Web of Science ®Google Scholar
• Jadli AS, Ballasy N, Edalat P, et al. Inside(sight) of tiny communicator: exosome biogenesis, secretion, and uptake. Mol Cell Biochem. 2020 Apr;467(1–2):77–94.
   PubMed Web of Science ®Google Scholar
• Frankel EB, Audhya A. ESCRT-dependent cargo sorting at multivesicular endosomes. Semin Cell Dev Biol. 2018 Feb;74:4–10.
   PubMed Web of Science ®Google Scholar
• Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020 Feb 7;367(6478):eaau6977.
   PubMed Web of Science ®Google Scholar
• Gluszko A, Szczepanski MJ, Ludwig N, et al. Exosomes in cancer: circulating immune-related biomarkers. Biomed Res Int. 2019;2019:1628029.
   PubMed Web of Science ®Google Scholar
• Mathieu M, Martin-Jaular L, Lavieu G, et al. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019 Jan;21(1):9–17.
   PubMed Web of Science ®Google Scholar
• Hoshino A, Costa-Silva B, Shen TL, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015 Nov 19;527(7578):329–335.
   PubMed Web of Science ®Google Scholar
• Whiteside TL. The emerging role of plasma exosomes in diagnosis, prognosis and therapies of patients with cancer. Contemp Oncol (Pozn). 2018 Mar;22:(1A):38–40.
   PubMedGoogle Scholar
• Camussi G, Deregibus MC, Bruno S, et al. Exosome/microvesicle-mediated epigenetic reprogramming of cells. Am J Cancer Res. 2011;1(1):98–110.
   PubMed Web of Science ®Google Scholar
• Muller L, Mitsuhashi M, Simms P, et al. Tumor-derived exosomes regulate expression of immune function-related genes in human T cell subsets. Sci Rep. 2016 Feb;4(6):20254.
   Web of Science ®Google Scholar
• Yang D, Zhang W, Zhang H, et al. Progress, opportunity, and perspective on exosome isolation - efforts for efficient exosome-based theranostics. Theranostics. 2020;10(8):3684–3707.
   PubMed Web of Science ®Google Scholar
• Purushothaman A. Exosomes from cell culture-conditioned medium: isolation by ultracentrifugation and characterization. Methods Mol Biol. 2019;1952:233–244.
   PubMedGoogle Scholar
• Johnstone RM, Adam M, Hammond JR, et al. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem. 1987 Jul 5;262(19):9412–9420.
   PubMed Web of Science ®Google Scholar
• Thery C, Amigorena S, Raposo G, et al. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol. 2006 Apr: Chapter 3:unit 3.22.
   PubMedGoogle Scholar
• Linares R, Tan S, Gounou C, et al. High-speed centrifugation induces aggregation of extracellular vesicles. J Extracell Vesicles. 2015;4:29509.
   PubMed Web of Science ®Google Scholar
• Mol EA, Goumans MJ, Doevendans PA, et al. Higher functionality of extracellular vesicles isolated using size-exclusion chromatography compared to ultracentrifugation. Nanomedicine. 2017 Aug;13(6):2061–2065.
   PubMed Web of Science ®Google Scholar
• Paolini L, Zendrini A, Di Noto G, et al. Residual matrix from different separation techniques impacts exosome biological activity. Sci Rep. 2016 Mar;24(6):23550.
   Web of Science ®Google Scholar
• Lim YJ, Lee SJ. Are exosomes the vehicle for protein aggregate propagation in neurodegenerative diseases? Acta Neuropathol Commun. 2017 Aug 29;5(1):64.
   PubMed Web of Science ®Google Scholar
• Simonsen JB. What are we looking at? Extracellular vesicles, lipoproteins, or both? Circ Res. 2017 Sep 29;121(8):920–922.
   PubMed Web of Science ®Google Scholar
• Sodar BW, Kittel A, Paloczi K, et al. Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection. Sci Rep. 2016 Apr;18(6):24316.
   Web of Science ®Google Scholar
• Karimi N, Cvjetkovic A, Jang SC, et al. Detailed analysis of the plasma extracellular vesicle proteome after separation from lipoproteins. Cell Mol Life Sci. 2018 Aug;75(15):2873–2886.
   PubMed Web of Science ®Google Scholar
• Gamez-Valero A, Monguio-Tortajada M, Carreras-Planella L, et al. Size-exclusion chromatography-based isolation minimally alters extracellular vesicles’ characteristics compared to precipitating agents. Sci Rep. 2016 Sep;19(6):33641.
   Web of Science ®Google Scholar
• An M, Wu J, Zhu J, et al. Comparison of an optimized ultracentrifugation method versus size-exclusion chromatography for isolation of exosomes from human serum. J Proteome Res. 2018 Oct 5;17(10):3599–3605.
   PubMed Web of Science ®Google Scholar
• Hong CS, Funk S, Whiteside TL. Isolation of biologically active exosomes from plasma of patients with cancer. Methods Mol Biol. 2017;1633:257–265.
   PubMedGoogle Scholar
• Shu S, Yang Y, Allen CL, et al. Purity and yield of melanoma exosomes are dependent on isolation method. J Extracell Vesicles. 2020;9(1):1692401.
   PubMed Web of Science ®Google Scholar
• Rood IM, Deegens JK, Merchant ML, et al. Comparison of three methods for isolation of urinary microvesicles to identify biomarkers of nephrotic syndrome. Kidney Int. 2010 Oct;78(8):810–816.
   PubMed Web of Science ®Google Scholar
• Ayala-Mar S, Donoso-Quezada J, Gallo-Villanueva RC, et al. Recent advances and challenges in the recovery and purification of cellular exosomes. Electrophoresis. 2019 Dec;40(23–24):3036–3049.
   PubMed Web of Science ®Google Scholar
• Van Deun J, Mestdagh P, Sormunen R, et al. The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling. J Extracell Vesicles. 2018;v3:24858.
   Google Scholar
• Whiteside TL. Tumor-derived exosomes and their role in cancer progression. Adv Clin Chem. 2016;74:103–141.
   PubMed Web of Science ®Google Scholar
• Sharma P, Ludwig S, Muller L, et al. Immunoaffinity-based isolation of melanoma cell-derived exosomes from plasma of patients with melanoma. J Extracell Vesicles. 2018;7(1):1435138.
   PubMed Web of Science ®Google Scholar
• Yerneni SS, Whiteside TL, Weiss LE, et al. Bioprinting exosome-like extracellular vesicle microenvironments. Bioprinting. 2019;13:e00041.
   Google Scholar
• Morales-Kastresana A, Jones JC. Flow cytometric analysis of extracellular vesicles. Methods Mol Biol. 2017;1545:215–225.
   PubMedGoogle Scholar
• Theodoraki MN, Hoffmann TK, Whiteside TL. Separation of plasma-derived exosomes into CD3((+)) and CD3((-)) fractions allows for association of immune cell and tumour cell markers with disease activity in HNSCC patients. Clin Exp Immunol. 2018 Jun;192(3):271–283.
   PubMed Web of Science ®Google Scholar
• Theodoraki MN, Yerneni SS, Hoffmann TK, et al. Clinical significance of PD-L1(+) exosomes in plasma of head and neck cancer patients. Clin Cancer Res. 2018 Feb 15;24(4):896–905.
   PubMed Web of Science ®Google Scholar
• Theodoraki MN, Hong CS, Donnenberg VS, et al. Evaluation of exosome proteins by on-bead flow cytometry. Cytometry A. 2020. In press. DOI:https://doi.org/10.1002/cyto.a.24193
   Google Scholar
• Fan Y, Duan X, Zhao M, et al. High-sensitive and multiplex biosensing assay of NSCLC-derived exosomes via different recognition sites based on SPRi array. Biosens Bioelectron. 2020 Apr;15(154):112066.
   Web of Science ®Google Scholar
• Baek R, Jorgensen MM. Multiplexed phenotyping of small extracellular vesicles using protein microarray (EV array). Methods Mol Biol. 2017;1545:117–127.
   PubMedGoogle Scholar
• Belov L, Matic KJ, Hallal S, et al. Extensive surface protein profiles of extracellular vesicles from cancer cells may provide diagnostic signatures from blood samples. J Extracell Vesicles. 2016;5:25355.
   PubMed Web of Science ®Google Scholar
• Welton JL, Brennan P, Gurney M, et al. Proteomics analysis of vesicles isolated from plasma and urine of prostate cancer patients using a multiplex, aptamer-based protein array. J Extracell Vesicles. 2016;5:31209.
   PubMed Web of Science ®Google Scholar
• Tian X, Shen H, Li Z, et al. Tumor-derived exosomes, myeloid-derived suppressor cells, and tumor microenvironment. J Hematol Oncol. 2019 Aug 22;12(1):84.
   PubMed Web of Science ®Google Scholar
• Razzo BM, Ludwig N, Hong CS, et al. Tumor-derived exosomes promote carcinogenesis of murine oral squamous cell carcinoma. Carcinogenesis. 2020;41:625–633.
   Web of Science ®Google Scholar
• Ludwig N, Yerneni SS, Razzo BM, et al. Exosomes from HNSCC promote angiogenesis through reprogramming of endothelial cells. Mol Cancer Res. 2018 Nov;16(11):1798–1808.
   PubMed Web of Science ®Google Scholar
• Hirata E, Sahai E. Tumor microenvironment and differential responses to therapy. Csh Perspect Med. 2017;Jul(7):7.
   Google Scholar
• Hinshaw DC, Shevde LA. The tumor microenvironment innately modulates cancer progression. Cancer Res. 2019 Sep 15;79(18):4557–4566.
   PubMed Web of Science ®Google Scholar
• Kim H, Lee S, Shin E, et al. The emerging roles of exosomes as EMT regulators in cancer. Cells. 2020 2; 9(4): Apr.
   Web of Science ®Google Scholar
• Schuler PJ, Saze Z, Hong CS, et al. Human CD4(+) CD39(+) regulatory T cells produce adenosine upon co-expression of surface CD73 or contact with CD73(+) exosomes or CD73(+) cells. Clin Exp Immunol. 2014 Aug;177(2):531–543.
   PubMed Web of Science ®Google Scholar
• Qin X, Guo H, Wang X, et al. Exosomal miR-196a derived from cancer-associated fibroblasts confers cisplatin resistance in head and neck cancer through targeting CDKN1B and ING5. Genome Biol. 2019 Jan 14;20(1):12.
   PubMed Web of Science ®Google Scholar
• Peinado H, Aleckovic M, Lavotshkin S, et al. Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med. 2012 Jun;18(6):883–891.
   PubMed Web of Science ®Google Scholar
• Zhou X, Yan T, Huang C, et al. Melanoma cell-secreted exosomal miR-155-5p induce proangiogenic switch of cancer-associated fibroblasts via SOCS1/JAK2/STAT3 signaling pathway. J Exp Clin Cancer Res. 2018 Oct 3;37(1):242.
   PubMed Web of Science ®Google Scholar
• Hu T, Hu J. Melanoma-derived exosomes induce reprogramming fibroblasts into cancer-associated fibroblasts via Gm26809 delivery. Cell Cycle. 2019 Nov;18(22):3085–3094.
   PubMed Web of Science ®Google Scholar
• Melo SA, Sugimoto H, O’Connell JT, et al. Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell. 2014 Nov 10;26(5):707–721.
   PubMed Web of Science ®Google Scholar
• Zhang HG, Kim H, Liu C, et al. Curcumin reverses breast tumor exosomes mediated immune suppression of NK cell tumor cytotoxicity. Biochim Biophys Acta. 2007 Jul;1773(7):1116–1123.
   PubMed Web of Science ®Google Scholar
• Theodoro TR, Matos LL, Cavalheiro RP, et al. Crosstalk between tumor cells and lymphocytes modulates heparanase expression. J Transl Med. 2019 Mar 29;17(1):103.
   PubMed Web of Science ®Google Scholar
• Yan W, Wu X, Zhou W, et al. Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells. Nat Cell Biol. 2018 May;20(5):597–609.
   PubMed Web of Science ®Google Scholar
• Feng W, Dean DC, Hornicek FJ, et al. Exosomes promote pre-metastatic niche formation in ovarian cancer. Mol Cancer. 2019 Aug 13;18(1):124.
   PubMed Web of Science ®Google Scholar
• Yi H, Ye J, Yang XM, et al. High-grade ovarian cancer secreting effective exosomes in tumor angiogenesis. Int J Clin Exp Pathol. 2015;8(5):5062–5070.
   PubMed Web of Science ®Google Scholar
• Cho JA, Park H, Lim EH, et al. Exosomes from ovarian cancer cells induce adipose tissue-derived mesenchymal stem cells to acquire the physical and functional characteristics of tumor-supporting myofibroblasts. Gynecol Oncol. 2011 Nov;123(2):379–386.
   PubMed Web of Science ®Google Scholar
• Huang Z, Yang M, Li Y, et al. Exosomes derived from hypoxic colorectal cancer cells transfer Wnt4 to normoxic cells to elicit a prometastatic phenotype. Int J Biol Sci. 2018;14(14):2094–2102.
   PubMed Web of Science ®Google Scholar
• Cooks T, Pateras IS, Jenkins LM, et al. Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246. Nat Commun. 2018 Feb 22;9(1):771.
   PubMed Web of Science ®Google Scholar
• Hu HY, Yu CH, Zhang HH, et al. Exosomal miR-1229 derived from colorectal cancer cells promotes angiogenesis by targeting HIPK2. Int J Biol Macromol. 2019 Jul 1;132:470–477.
   PubMed Web of Science ®Google Scholar
• Yoshii S, Hayashi Y, Iijima H, et al. Exosomal microRNAs derived from colon cancer cells promote tumor progression by suppressing fibroblast TP53 expression. Cancer Sci. 2019 Aug;110(8):2396–2407.
   PubMed Web of Science ®Google Scholar
• Hornick NI, Doron B, Abdelhamed S, et al. AML suppresses hematopoiesis by releasing exosomes that contain microRNAs targeting c-MYB. Sci Signal. 2016 Sep 6;9(444):ra88.
   PubMed Web of Science ®Google Scholar
• Wang B, Wang X, Hou D, et al. Exosomes derived from acute myeloid leukemia cells promote chemoresistance by enhancing glycolysis-mediated vascular remodeling. J Cell Physiol. 2019 Jul;234(7):10602–10614.
   PubMed Web of Science ®Google Scholar
• Chen T, Zhang G, Kong L, et al. Leukemia-derived exosomes induced IL-8 production in bone marrow stromal cells to protect the leukemia cells against chemotherapy. Life Sci. 2019 Mar 15;221:187–195.
   PubMed Web of Science ®Google Scholar
• Azambuja JH, Ludwig N, Yerneni SS, et al. Arginase-1+ exosomes from reprogrammed macrophages promote glioblastoma progression. Int J Mol Sci. 2020 Jun 2;21:11.
   Web of Science ®Google Scholar
• Ludwig S, Sharma P, Theodoraki MN, et al. Molecular and functional profiles of exosomes from HPV(+) and HPV(-) head and neck cancer cell lines. Front Oncol. 2018;8:445.
   PubMed Web of Science ®Google Scholar
• Ludwig S, Floros T, Theodoraki MN, et al. Suppression of lymphocyte functions by plasma exosomes correlates with disease activity in patients with head and neck cancer. Clin Cancer Res. 2017 Aug 15;23(16):4843–4854.
   PubMed Web of Science ®Google Scholar
• Theodoraki MN, Matsumoto A, Beccard I, et al. CD44v3 protein-carrying tumor-derived exosomes in HNSCC patients’ plasma as potential noninvasive biomarkers of disease activity. Oncoimmunology. 2020;9(1):1747732.
   PubMed Web of Science ®Google Scholar
• Theodoraki MN, Yerneni S, Gooding WE, et al. Circulating exosomes measure responses to therapy in head and neck cancer patients treated with cetuximab, ipilimumab, and IMRT. Oncoimmunology. 2019;8(7):1593805.
   PubMed Web of Science ®Google Scholar
• Szajnik M, Derbis M, Lach M, et al. Exosomes in plasma of patients with ovarian carcinoma: potential biomarkers of tumor progression and response to therapy. Gynecol Obstet (Sunnyvale). 2013 Apr 29;(Suppl 4):003.
   PubMedGoogle Scholar
• Syn N, Wang L, Sethi G, et al. Exosome-mediated metastasis: from epithelial-mesenchymal transition to escape from immunosurveillance. Trends Pharmacol Sci. 2016 Jul;37(7):606–617.
   PubMed Web of Science ®Google Scholar
• Theodoraki MN, Yerneni SS, Brunner C, et al. Plasma-derived exosomes reverse epithelial-to-mesenchymal transition after photodynamic therapy of patients with head and neck cancer. Oncoscience. 2018 Mar;5(3–4):75–87.
   PubMedGoogle Scholar
• Choi D, Spinelli C, Montermini L, et al. Oncogenic regulation of extracellular vesicle proteome and heterogeneity. Proteomics. 2019 Jan;19(1–2):e1800169.
   PubMed Web of Science ®Google Scholar
• Muller L, Simms P, Hong CS, et al. Human tumor-derived exosomes (TEX) regulate Treg functions via cell surface signaling rather than uptake mechanisms. Oncoimmunology. 2017;6(8):e1261243.
   PubMed Web of Science ®Google Scholar
• Hong CS, Funk S, Muller L, et al. Isolation of biologically active and morphologically intact exosomes from plasma of patients with cancer. J Extracell Vesicles. 2016;5:29289.
   PubMed Web of Science ®Google Scholar
• Hong CS, Muller L, Whiteside TL, et al. Plasma exosomes as markers of therapeutic response in patients with acute myeloid leukemia. Front Immunol. 2014;5:160.
   PubMed Web of Science ®Google Scholar
• Chen G, Huang AC, Zhang W, et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 2018 Aug;560(7718):382–386.
   PubMed Web of Science ®Google Scholar
• Chalmin F, Ladoire S, Mignot G, et al. Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J Clin Invest. 2010 Feb;120(2):457–471.
   PubMed Web of Science ®Google Scholar
• Xiang X, Poliakov A, Liu C, et al. Induction of myeloid-derived suppressor cells by tumor exosomes. Int J Cancer. 2009 Jun 1;124(11):2621–2633.
   PubMed Web of Science ®Google Scholar
• Himes BT, Peterson TE, de Mooij T, et al. The role of extracellular vesicles and PD-L1 in glioblastoma-mediated immunosuppressive monocyte induction. Neuro Oncol. 2020 Feb 21;22(7):967–978.
   PubMed Web of Science ®Google Scholar
• Liu Y, Xiang X, Zhuang X, et al. Contribution of MyD88 to the tumor exosome-mediated induction of myeloid derived suppressor cells. Am J Pathol. 2010 May;176(5):2490–2499.
   PubMed Web of Science ®Google Scholar
• Guo X, Qiu W, Wang J, et al. Glioma exosomes mediate the expansion and function of myeloid-derived suppressor cells through microRNA-29a/Hbp1 and microRNA-92a/Prkar1a pathways. Int J Cancer. 2019 Jun 15;144(12):3111–3126.
   PubMed Web of Science ®Google Scholar
• Guo X, Qiu W, Liu Q, et al. Immunosuppressive effects of hypoxia-induced glioma exosomes through myeloid-derived suppressor cells via the miR-10a/Rora and miR-21/Pten Pathways. Oncogene. 2018 Aug;37(31):4239–4259.
   PubMed Web of Science ®Google Scholar
• Huber V, Vallacchi V, Fleming V, et al. Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma. J Clin Invest. 2018 Dec 3;128(12):5505–5516.
   PubMed Web of Science ®Google Scholar
• Ohue Y, Nishikawa H. Regulatory T (Treg) cells in cancer: can Treg cells be a new therapeutic target? Cancer Sci. 2019 Jul;110(7):2080–2089.
   PubMed Web of Science ®Google Scholar
• Szajnik M, Czystowska M, Szczepanski MJ, et al. Tumor-derived microvesicles induce, expand and up-regulate biological activities of human regulatory T cells (Treg). PLoS One. 2010 Jul 22;5(7):e11469.
   PubMed Web of Science ®Google Scholar
• Schuler PJ, Saze Z, Hong CS, et al. Human CD4+ CD39+ regulatory T cells produce adenosine upon co-expression of surface CD73 or contact with CD73+ exosomes or CD73+ cells. Clin Exp Immunol. 2014 Aug;177(2):531–543.
   PubMed Web of Science ®Google Scholar
• Mrizak D, Martin N, Barjon C, et al. Effect of nasopharyngeal carcinoma-derived exosomes on human regulatory T cells. J Natl Cancer Inst. 2015 Jan;107(1):363.
   PubMedGoogle Scholar
• Wieckowski E, Whiteside TL. Human tumor-derived vs dendritic cell-derived exosomes have distinct biologic roles and molecular profiles. Immunol Res. 2006;36(1–3):247–254.
   PubMed Web of Science ®Google Scholar
• Taylor DD, Gercel-Taylor C, Lyons KS, et al. T-cell apoptosis and suppression of T-cell receptor/CD3-zeta by Fas ligand-containing membrane vesicles shed from ovarian tumors. Clin Cancer Res. 2003 Nov 1;9(14):5113–5119.
   PubMed Web of Science ®Google Scholar
• Upreti D, Zhang ML, Bykova E, et al. Change in CD3zeta-chain expression is an independent predictor of disease status in head and neck cancer patients. Int J Cancer. 2016 Jul 1;139(1):122–129.
   PubMed Web of Science ®Google Scholar
• Gruber IV, El Yousfi S, Durr-Storzer S, et al. Down-regulation of CD28, TCR-zeta (zeta) and up-regulation of FAS in peripheral cytotoxic T-cells of primary breast cancer patients. Anticancer Res. 2008 Mar-Apr;28(2A):779–784.
   PubMed Web of Science ®Google Scholar
• Czystowska-Kuzmicz M, Sosnowska A, Nowis D, et al. ** Small extracellular vesicles containing arginase-1 suppress T-cell responses and promote tumor growth in ovarian carcinoma. Nat Commun. 2019 Jul 5;10(1):3000.
   PubMed Web of Science ®Google Scholar
• Clayton A, Mitchell JP, Court J, et al. Human tumor-derived exosomes selectively impair lymphocyte responses to interleukin-2. Cancer Res. 2007 Aug 1;67(15):7458–7466.
   PubMed Web of Science ®Google Scholar
• Wieckowski EU, Visus C, Szajnik M, et al. * Tumor-derived microvesicles promote regulatory T cell expansion and induce apoptosis in tumor-reactive activated CD8+ T lymphocytes. J Immunol. 2009 Sep 15;183(6):3720–3730.
   PubMed Web of Science ®Google Scholar
• Whiteside TL. Immune modulation of T-cell and NK (natural killer) cell activities by TEXs (tumour-derived exosomes). Biochem Soc Trans. 2013 Feb 1;41(1):245–251.
   PubMed Web of Science ®Google Scholar
• Rivoltini L, Chiodoni C, Squarcina P, et al. TNF-related apoptosis-inducing ligand (TRAIL)-armed exosomes deliver proapoptotic signals to tumor site. Clin Cancer Res. 2016 Jul 15;22(14):3499–3512.
   PubMed Web of Science ®Google Scholar
• Peng P, Yan Y, Keng S. Exosomes in the ascites of ovarian cancer patients: origin and effects on anti-tumor immunity. Oncol Rep. 2011 Mar;25(3):749–762.
   PubMed Web of Science ®Google Scholar
• Kim DH, Kim H, Choi YJ, et al. Exosomal PD-L1 promotes tumor growth through immune escape in non-small cell lung cancer. Exp Mol Med. 2019 Aug 9;51(8):1–13.
   Web of Science ®Google Scholar
• Czystowska M, Szczepanski MJ, Szajnik M, et al. Mechanisms of T-cell protection from death by IRX-2: a new immunotherapeutic. Cancer Immunol Immunother. 2011 Apr;60(4):495–506.
   PubMed Web of Science ®Google Scholar
• Daassi D, Mahoney KM, Freeman GJ. ** The importance of exosomal PDL1 in tumour immune evasion. Nat Rev Immunol. 2020 Apr;20(4):209–215.
   PubMed Web of Science ®Google Scholar
• Liu C, Yu S, Zinn K, et al. Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function. J Immunol. 2006 Feb 1;176(3):1375–1385.
   PubMed Web of Science ®Google Scholar
• MJ S, Szajnik M, Welsh A, et al. Blast-derived microvesicles in sera from patients with acute myeloid leukemia suppress natural killer cell function via membrane-associated transforming growth factor-beta1. Haematologica. 2011 Sep;96(9):1302–1309.
   PubMed Web of Science ®Google Scholar
• Xia Y, Zhang Q, Zhen Q, et al. Negative regulation of tumor-infiltrating NK cell in clear cell renal cell carcinoma patients through the exosomal pathway. Oncotarget. 2017 Jun 6;8(23):37783–37795.
   PubMedGoogle Scholar
• Hedlund M, Nagaeva O, Kargl D, et al. Thermal- and oxidative stress causes enhanced release of NKG2D ligand-bearing immunosuppressive exosomes in leukemia/lymphoma T and B cells. PLoS One. 2011 Feb 25;6(2):e16899.
   PubMed Web of Science ®Google Scholar
• Lundholm M, Schroder M, Nagaeva O, et al. Prostate tumor-derived exosomes down-regulate NKG2D expression on natural killer cells and CD8+ T cells: mechanism of immune evasion. PLoS One. 2014;9(9):e108925.
   PubMed Web of Science ®Google Scholar
• Labani-Motlagh A, Israelsson P, Ottander U, et al. Differential expression of ligands for NKG2D and DNAM-1 receptors by epithelial ovarian cancer-derived exosomes and its influence on NK cell cytotoxicity. Tumour Biol. 2016 Apr;37(4):5455–5466.
   PubMedGoogle Scholar
• Ashiru O, Boutet P, Fernandez-Messina L, et al. Natural killer cell cytotoxicity is suppressed by exposure to the human NKG2D ligand MICA*008 that is shed by tumor cells in exosomes. Cancer Res. 2010 Jan 15;70(2):481–489.
   PubMed Web of Science ®Google Scholar
• Fernandez-Messina L, Ashiru O, Boutet P, et al. Differential mechanisms of shedding of the glycosylphosphatidylinositol (GPI)-anchored NKG2D ligands. J Biol Chem. 2010 Mar 19;285(12):8543–8551.
   PubMed Web of Science ®Google Scholar
• Baig MS, Roy A, Rajpoot S, et al. Tumor-derived exosomes in the regulation of macrophage polarization. Inflamm Res. 2020 May;69(5):435–451.
   PubMed Web of Science ®Google Scholar
• Wolf-Dennen K, Gordon N, Kleinerman ES. Exosomal communication by metastatic osteosarcoma cells modulates alveolar macrophages to an M2 tumor-promoting phenotype and inhibits tumoricidal functions. Oncoimmunology. 2020;9(1):1747677.
   PubMed Web of Science ®Google Scholar
• Ying X, Wu Q, Wu X, et al. Epithelial ovarian cancer-secreted exosomal miR-222-3p induces polarization of tumor-associated macrophages. Oncotarget. 2016 Jul 12;7(28):43076–43087.
   PubMedGoogle Scholar
• Gerloff D, Lutzkendorf J, Moritz RKC, et al. Melanoma-derived exosomal miR-125b-5p educates tumor associated macrophages (TAMs) by targeting lysosomal acid lipase A (LIPA). Cancers (Basel). 2020 Feb 17;12(2):464.
   PubMed Web of Science ®Google Scholar
• Wang D, Wang X, Si M, et al. Exosome-encapsulated miRNAs contribute to CXCL12/CXCR4-induced liver metastasis of colorectal cancer by enhancing M2 polarization of macrophages. Cancer Lett. 2020 Apr 1;474:36–52.
   PubMed Web of Science ®Google Scholar
• Taghikhani A, Farzaneh F, Sharifzad F, et al. Engineered tumor-derived extracellular vesicles: potentials in cancer Immunotherapy. Front Immunol. 2020;11:221.
   PubMed Web of Science ®Google Scholar
• Whiteside TL. The effect of tumor-derived exosomes on immune regulation and cancer immunotherapy. Future Oncol. 2017 Dec;13(28):2583–2592.
   PubMed Web of Science ®Google Scholar
• Hood JL. Melanoma exosomes enable tumor tolerance in lymph nodes. Med Hypotheses. 2016 May;90:11–13.
   PubMed Web of Science ®Google Scholar
• Poggio M, Hu T, Pai CC, et al. ** Suppression of exosomal PD-L1 induces systemic anti-tumor immunity and memory. Cell. 2019 Apr 4;177(2):414–427 e13.
   PubMed Web of Science ®Google Scholar
• Theodoraki MN, Hoffmann TK, Jackson EK, et al. Exosomes in HNSCC plasma as surrogate markers of tumour progression and immune competence. Clin Exp Immunol. 2018 Oct;194(1):67–78.
   PubMed Web of Science ®Google Scholar
• Wu D, Yan J, Shen X, et al. Profiling surface proteins on individual exosomes using a proximity barcoding assay. Nat Commun. 2019 Aug 26;10(1):3854.
   PubMed Web of Science ®Google Scholar
• Orme JJ, Jazieh KA, Xie T, et al. ADAM10 and ADAM17 cleave PD-L1 to mediate PD-(L)1 inhibitor resistance. Oncoimmunology. 2020;9(1):1744980.
   PubMed Web of Science ®Google Scholar
• Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015 Apr 3;348(6230):56–61.
   PubMed Web of Science ®Google Scholar
• Fritz JM, Lenardo MJ. Development of immune checkpoint therapy for cancer. J Exp Med. 2019 Jun 3;216(6):1244–1254.
   PubMed Web of Science ®Google Scholar
• Zhang JY, Yan YY, Li JJ, et al. PD-1/PD-L1 based combinational cancer therapy: icing on the cake. Front Pharmacol. 2020;11:722.
   PubMed Web of Science ®Google Scholar
• Marin-Acevedo JA, Dholaria B, Soyano AE, et al. Next generation of immune checkpoint therapy in cancer: new developments and challenges. J Hematol Oncol. 2018 Mar 15;11(1):39.
   PubMed Web of Science ®Google Scholar
• Bai J, Gao Z, Li X, et al. Regulation of PD-1/PD-L1 pathway and resistance to PD-1/PD-L1 blockade. Oncotarget. 2017 Dec 15;8(66):110693–110707.
   PubMedGoogle Scholar
• Wu P, Wu D, Li L, et al. PD-L1 and survival in solid tumors: a meta-analysis. PLoS One. 2015;10(6):e0131403.
   PubMed Web of Science ®Google Scholar
• Sharma P, Callahan MK, Bono P, et al. Nivolumab monotherapy in recurrent metastatic urothelial carcinoma (CheckMate 032): a multicentre, open-label, two-stage, multi-arm, phase 1/2 trial. Lancet Oncol. 2016 Nov;17(11):1590–1598.
   PubMed Web of Science ®Google Scholar
• Tang Y, Zhang P, Wang Y, et al. The Biogenesis, biology, and clinical significance of exosomal PD-L1 in cancer. Front Immunol. 2020;11:604.
   PubMed Web of Science ®Google Scholar
• Raimondo S, Pucci M, Alessandro R, et al. Extracellular vesicles and tumor-immune escape: biological functions and clinical perspectives. Int J Mol Sci. 2020 Mar 26;21(7):2286.
   Web of Science ®Google Scholar
• Ricklefs FL, Alayo Q, Krenzlin H, et al. Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles. Sci Adv. 2018 Mar 4;4(3):eaar2766.
   PubMed Web of Science ®Google Scholar
• Yang Y, Li CW, Chan LC, et al. Exosomal PD-L1 harbors active defense function to suppress T cell killing of breast cancer cells and promote tumor growth. Cell Res. 2018 Aug;28(8):862–864.
   PubMed Web of Science ®Google Scholar
• Zhou J, Mahoney KM, Giobbie-Hurder A, et al. Soluble PD-L1 as a biomarker in malignant melanoma treated with checkpoint blockade. Cancer Immunol Res. 2017 Jun;5(6):480–492.
   PubMed Web of Science ®Google Scholar
• Hong CS, Danet-Desnoyers G, Shan X, et al. Human acute myeloid leukemia blast-derived exosomes in patient-derived xenograft mice mediate immune suppression. Exp Hematol. 2019 Aug;76(60–66):e2.
   Google Scholar
• Cordonnier M, Nardin C, Chanteloup G, et al. ** Tracking the evolution of circulating exosomal-PD-L1 to monitor melanoma patients. J Extracell Vesicles. 2020;9(1):1710899.
   PubMed Web of Science ®Google Scholar
• Sharma P, Diergaarde B, Ferrone S, et al. *** Melanoma cell-derived exosomes in plasma of melanoma patients suppress functions of immune effector cells. Sci Rep. 2020 Jan 9;10(1):92.
   PubMed Web of Science ®Google Scholar
• Whiteside TL. The potential of tumor-derived exosomes for noninvasive cancer monitoring: an update. Expert Rev Mol Diagn. 2018 Dec;18(12):1029–1040.
   PubMed Web of Science ®Google Scholar
• Hong CS, Sharma P, Yerneni SS, et al. Circulating exosomes carrying an immunosuppressive cargo interfere with cellular immunotherapy in acute myeloid leukemia. Sci Rep. 2017 Oct 31;7(1):14684.
   PubMed Web of Science ®Google Scholar
• Aung T, Chapuy B, Vogel D, et al. Exosomal evasion of humoral immunotherapy in aggressive B-cell lymphoma modulated by ATP-binding cassette transporter A3 [Research Support, Non-U.S. Gov’t]. Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15336–15341.
   PubMed Web of Science ®Google Scholar
• Battke C, Ruiss R, Welsch U, et al. Tumour exosomes inhibit binding of tumour-reactive antibodies to tumour cells and reduce ADCC. Cancer Immunol Immunother. 2011 May;60(5):639–648.
   PubMed Web of Science ®Google Scholar
• Ciravolo V, Huber V, Ghedini GC, et al. Potential role of HER2-overexpressing exosomes in countering trastuzumab-based therapy. J Cell Physiol. 2012 Feb;227(2):658–667.
   PubMed Web of Science ®Google Scholar
• Capello M, Vykoukal JV, Katayama H, et al. Exosomes harbor B cell targets in pancreatic adenocarcinoma and exert decoy function against complement-mediated cytotoxicity. Nat Commun. 2019 Jan 16;10(1):254.
   PubMed Web of Science ®Google Scholar
• Nakajima K, Nangia-Makker P, Hogan V, et al. Cancer self-defense: an immune stealth. Cancer Res. 2017 Oct 15;77(20):5441–5444.
   PubMed Web of Science ®Google Scholar
• Muller L, Muller-Haegele S, Mitsuhashi M, et al. Exosomes isolated from plasma of glioma patients enrolled in a vaccination trial reflect antitumor immune activity and might predict survival. Oncoimmunology. 2015 Jun;4(6):e1008347.
   PubMed Web of Science ®Google Scholar
• Bergmann C, Strauss L, Wieckowski E, et al. Tumor-derived microvesicles in sera of patients with head and neck cancer and their role in tumor progression. Head Neck. 2009 Mar;31(3):371–380.
   PubMed Web of Science ®Google Scholar
• Kim JW, Wieckowski E, Taylor DD, et al. Fas ligand-positive membranous vesicles isolated from sera of patients with oral cancer induce apoptosis of activated T lymphocytes. Clin Cancer Res. 2005 Feb 1;11(3):1010–1020.
   PubMed Web of Science ®Google Scholar
• Hong CS, Muller L, Boyiadzis M, et al. Isolation and characterization of CD34+ blast-derived exosomes in acute myeloid leukemia. PLoS One. 2014;9(8):e103310.
   PubMed Web of Science ®Google Scholar
• Abramowicz A, Marczak L, Wojakowska A, et al. Harmonization of exosome isolation from culture supernatants for optimized proteomics analysis. PLoS One. 2018;13(10):e0205496.
   PubMed Web of Science ®Google Scholar
• Zebrowska A, Widlak P, Whiteside T, et al. Signaling of tumor-derived sEV impacts melanoma progression. Int J Mol Sci. 2020 Jul 17;21(14):5066.
   PubMed Web of Science ®Google Scholar
• Pietrowska M, Funk S, Gawin M, et al. Isolation of exosomes for the purpose of protein cargo analysis with the use of mass spectrometry. Methods Mol Biol. 2017;1654:291–307.
   PubMedGoogle Scholar
• Rahbarghazi R, Jabbari N, Sani NA, et al. Tumor-derived extracellular vesicles: reliable tools for cancer diagnosis and clinical applications. Cell Commun Signal. 2019 Jul 10;17(1):73.
   PubMed Web of Science ®Google Scholar
• Zhang S, Du L, Wang L, et al. Evaluation of serum exosomal LncRNA-based biomarker panel for diagnosis and recurrence prediction of bladder cancer. J Cell Mol Med. 2019 Feb;23(2):1396–1405.
   PubMed Web of Science ®Google Scholar
• Li M, Zou X, Xia T, et al. A five-miRNA panel in plasma was identified for breast cancer diagnosis. Cancer Med. 2019 Nov;8(16):7006–7017.
   PubMed Web of Science ®Google Scholar
• Yang YN, Zhang R, Du JW, et al. Predictive role of UCA1-containing exosomes in cetuximab-resistant colorectal cancer. Cancer Cell Int. 2018;18:164.
   PubMed Web of Science ®Google Scholar
• Lin XJ, Fang JH, Yang XJ, et al. Hepatocellular carcinoma cell-secreted exosomal MicroRNA-210 promotes angiogenesis in vitro and in vivo. Mol Ther Nucleic Acids. 2018 Jun 1;11:243–252.
   PubMedGoogle Scholar
• Cui Y, Xu HF, Liu MY, et al. Mechanism of exosomal microRNA-224 in development of hepatocellular carcinoma and its diagnostic and prognostic value. World J Gastroenterol. 2019 Apr 21;25(15):1890–1898.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Zhang Y, Yin Y, et al. Detection of circulating exosomal miR-17-5p serves as a novel non-invasive diagnostic marker for non-small cell lung cancer patients. Pathol Res Pract. 2019 Aug;215(8):152466.
   PubMed Web of Science ®Google Scholar
• Rodriguez Zorrilla S, Perez-Sayans M, Fais S, et al. A pilot clinical study on the prognostic relevance of plasmatic exosomes levels in oral squamous cell carcinoma patients. Cancers (Basel). 2019 Mar 26;11(3):429.
   PubMed Web of Science ®Google Scholar
• Su YY, Sun L, Guo ZR, et al. Upregulated expression of serum exosomal miR-375 and miR-1307 enhance the diagnostic power of CA125 for ovarian cancer. J Ovarian Res. 2019 Jan 22;12(1):6.
   PubMed Web of Science ®Google Scholar
• Buscail E, Alix-Panabieres C, Quincy P, et al. High clinical value of liquid biopsy to detect circulating tumor cells and tumor exosomes in pancreatic ductal adenocarcinoma patients eligible for up-front surgery. Cancers (Basel). 2019 Oct 26;11(11):1656.
   Web of Science ®Google Scholar