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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2017

Open Access 01-12-2017 | Review

The crosstalk between autophagic and endo-/exosomal pathways in antigen processing for MHC presentation in anticancer T cell immune responses

Authors: Liangshun You, Liping Mao, Juying Wei, Shenhe Jin, Chunmei Yang, Hui Liu, Li Zhu, Wenbin Qian

Published in: Journal of Hematology & Oncology | Issue 1/2017

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Abstract

T cells recognize antigen fragments from proteolytic products that are presented to them in the form of peptides on major histocompatibility complex (MHC) molecules, which is crucial for the T cell to identify infected or transformed cells. Autophagy, a process that delivers cytoplasmic constituents for lysosomal degradation, has been observed to provide a substantial source of intra- and extracellular antigens for MHC presentation to T cells, which will impact the tumor-specific immune response. Meanwhile, extracellular components are transported to cytoplasm for the degradation/secretion process by the endo-/exosomal pathway and are thus involved in multiple physiological and pathological processes, including immune responses. Autophagy and endo-/exosomal pathways are intertwined in a highly intricate manner and both are closely involved in antigen processing for MHC presentation; thus, we propose that they may coordinate in antigen processing and presentation in anticancer T cell immune responses. In this article, we discuss the molecular and functional crosstalk between autophagy and endo-/exosomal pathways and their contributions to antigen processing for MHC presentation in anticancer T cell immune responses.
Literature
1.
Varshavsky A. The ubiquitin system, autophagy, and regulated protein degradation. Annu Rev Biochem. 2017;86:123–8.PubMedCrossRef
2.
Mizushima N. Methods for monitoring autophagy. Int J Biochem Cell Biol. 2004;6(12):2491–502.CrossRef
3.
Ktistakis NT, Tooze SA. Digesting the expanding mechanisms of autophagy. Trends Cell Biol. 2016;26(8):624–35.PubMedCrossRef
4.
Levine B, Klionsky DJ. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev Cell. 2004;6(4):463–77.PubMedCrossRef
5.
Baixauli F, Lopez-Otin C, Mittelbrunn M. Exosomes and autophagy: coordinated mechanisms for the maintenance of cellular fitness. Front Immunol. 2014;5:403.PubMedPubMedCentralCrossRef
6.
7.
8.
Orvedahl A, Levine B. Eating the enemy within: autophagy in infectious diseases. Cell Death Differ. 2009;16(1):57–69.PubMedCrossRef
9.
Demirtas L, Guclu A, Erdur FM, Akbas EM, Ozcicek A, Onk D, et al. Apoptosis, autophagy & endoplasmic reticulum stress in diabetes mellitus. Indian J Med Res. 2016;44(4):515–24.
10.
11.
Zhang C, Syed TW, Liu R, Yu J. Role of endoplasmic reticulum stress, autophagy, and inflammation in cardiovascular disease. Front Cardiovasc Med. 2017;12:4–29.
12.
Yen WL, Klionsky DJ. How to live long and prosper: autophagy, mitochondria, and aging. Physiology (Bethesda). 2008;23:248–62.CrossRef
13.
14.
Yoshida GJ. Therapeutic strategies of drug repositioning targeting autophagy to induce cancer cell death: from pathophysiology to treatment. J Hematol Oncol. 2017;10:67.PubMedPubMedCentralCrossRef
15.
16.
Shibutani ST, Saitoh T, Nowag H, Münz C, Yoshimori T. Autophagy and autophagy-related proteins in the immune system. Nat Immunol. 2015;16(10):1014–24.PubMedCrossRef
17.
18.
You L, Jin S, Zhu L, Qian W. Autophagy, autophagy-associated adaptive immune responses and its role in hematologic malignancies. Oncotarget. 2017;8(7):12374–88.PubMed
19.
20.
Papandreou ME, Tavernarakis N. Autophagy and the endo/exosomal pathways in health and disease. Biotechnol J. 2017;12(1):e00175.CrossRef
21.
22.
23.
24.
25.
26.
Lamb CA, Yoshimori T, Tooze SA. The autophagosome: origins unknown, biogenesis complex. Nat Rev Mol Cell Biol. 2013;14(12):759–74.PubMedCrossRef
27.
Alemu EA, Lamark T, Torgersen KM, Birgisdottir AB, Larsen KB, Jain A, et al. ATG8 family proteins act as scaffolds for assembly of the ULK complex: sequence requirements for LC3-interacting region (LIR) motifs. J Biol Chem. 2012;287(47):39275–9.PubMedPubMedCentralCrossRef
28.
Young AR, Chan EY, Hu XW, Köchl R, Crawshaw SG, High S, et al. Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci. 2006;119(Pt18):3888–9000.PubMedCrossRef
29.
Axe EL, Walker SA, Manifava M, Chandra P, Roderick HL, Habermann A, et al. Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol. 2008;182(4):685–701.PubMedPubMedCentralCrossRef
30.
31.
Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 2007;8(9):741–52.PubMedCrossRef
32.
Sou YS, Waguri S, Iwata J, Ueno T, Fujimura T, Hara T, et al. The Atg8 conjugation system is indispensable for proper development of autophagic isolation membranes in mice. Mol Biol Cell. 2008;19(11):4762–75.PubMedPubMedCentralCrossRef
33.
Nakatogawa H, Suzuki K, Kamada Y, Ohsumi Y. Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat Rev Mol Cell Biol. 2009;10(7):458–67.PubMedCrossRef
34.
35.
Ojha CR, Lapierre J, Rodriguez M, Dever SM, Zadeh MA, DeMarino C, et al. Interplay between autophagy, exosomes and HIV-1 associated neurological disorders: new insights for diagnosis and therapeutic applications. Viruses. 2017;9(7):176.PubMedCentralCrossRef
36.
Griffiths RE, Kupzig S, Cogan N, Mankelow TJ, Betin VM, Trakarnsanga K, et al. Maturing reticulocytes internalize plasma membrane in glycophorin A-containing vesicles that fuse with autophagosomes before exocytosis. Autophagy. 2012;119(26):6296–306.
37.
Lamb CA, Dooley HC, Tooze SA. Endocytosis and autophagy: shared machinery for degradation. BioEssays. 2013;35(1):34–45.PubMedCrossRef
38.
Murrow L, Malhotra R, Debnath J. ATG12-ATG3 interacts with Alix to promote basal autophagic flux and late endosome function. Nat Cell Biol. 2015;17(3):300–10.PubMedPubMedCentralCrossRef
39.
Lee JA, Gao FB. Roles of ESCRT in autophagy-associated neurodegeneration. Autophagy. 2014;4(2):230–2.CrossRef
40.
Xavier M, Renaud L. Autophagy in endosomal mutants: desperately seeking to survive. WormBook. 2012;1:216–20.
41.
Lee J, Beigneux A, Ahmad ST, Gao FB. ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration. Current Biology Cb. 2007;17(4):1561–7.PubMedCrossRef
42.
Scott CC, Vacca F, Gruenberg J. Endosome maturation, transport and functions. Semin Cell Dev Biol. 2014;31(7):2–10.PubMedCrossRef
43.
Fader CM, Colombo MI. Autophagy and multivesicular bodies: two closely related partners. Cell Death Differ. 2009;16(1):70–8.PubMedCrossRef
44.
Fevrier B, Raposo G. Exosomes: endosomal-derived vesicles shipping extracellular messages. Curr Opin Cell Biol. 2004;16(4):415–21.PubMedCrossRef
45.
Fader C, Colombo MI. Multivesicular bodies and autophagy in erythrocyte maturation. Autophagy. 2006;2(2):122–5.PubMedCrossRef
46.
47.
Bhattacharya A, Eissa NT. Autophagy as a stress response pathway in the immune system. Int Rev Immunol. 2015;34(5):382–402.PubMedCrossRef
48.
Romao S, Gasser N, Becker AC, Guhl B, Bajagic M, Vanoaica D, et al. Autophagy proteins stabilize pathogen-containing phagosomes for prolonged MHC II antigen processing. J Cell Biol. 2013;203(5):757–66.PubMedPubMedCentralCrossRef
49.
Lee HK, Mattei LM, Steinberg BE, Alberts P, Lee YH, Chervonsky A, et al. In vivo requirement for Atg5 in antigen presentation by dendritic cells. Immunity. 2010;32(2):227–39.PubMedPubMedCentralCrossRef
50.
Delamarre L, Pack M, Chang H, Mellman I, Trombetta ES. Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate. Science. 2005;307(5715):1630–4.PubMedCrossRef
51.
Jin Y, Hong Y, Park CY, Hong Y. Molecular interactions of autophagy with the immune system and cancer. Int J Mol Sci. 2017;18:e1694.PubMedCrossRef
52.
Schmid D, Pypaert M, Münz C. Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity. 2007;26(1):79–92.PubMedCrossRef
53.
54.
Dörfel D, Appel S, Grünebach F, Weck MM, Müller MR, Heine A, et al. Processing and presentation of HLA class I and II epitopes by dendritic cells after transfection with in vitro-transcribed MUC1 RNA. Blood. 2005;105(8):3199–205.PubMedCrossRef
55.
Brazil MI, Weiss S, Stockinger B. Excessive degradation of intracellular protein in macrophages prevents presentation in the context of major histocompatibility complex class II molecules. Eur J Immunol. 1997;27(6):1506–14.PubMedCrossRef
56.
Liu S, Yin L, Stroopinsky D, Rajabi H, Puissant A, Stegmaier K, et al. MUC1-C oncoprotein promotes FLT3 receptor activation in acute myeloid leukemia cells. Blood. 2014;123(5):734–42.PubMedPubMedCentralCrossRef
57.
58.
Bell C, English L, Boulais J, Chemali M, Caron-Lizotte O, Desjardins M, et al. Quantitative proteomics reveals the induction of mitophagy in tumor necrosis factor-α-activated (TNFα) macrophages. Mol Cell Proteomics. 2013;12(9):2394–407.PubMedPubMedCentralCrossRef
59.
Li X, Wang S, Zhu R, Li H, Han Q, Zhao RC. Lung tumor exosomes induce a pro-inflammatory phenotype in mesenchymal stem cells via NFκB-TLR signaling pathway. J Hematol Oncol. 2016;9:42.PubMedPubMedCentralCrossRef
60.
Thery C, Ostrowski M, Segura E. Membrane vesicles as conveyors of immune responses. Nat Rev Immunol. 2009;9(8):581–93.PubMedCrossRef
61.
Lou G, Song X, Yang F, Wu S, Wang J, Chen Z, Liu Y. Exosomes derived from miR-122-modified adipose tissue-derived MSCs increase chemosensitivity of hepatocellular carcinoma. J Hematol Oncol. 2015;8:122.PubMedPubMedCentralCrossRef
62.
Soung YH, Ford S, Zhang V, Chung J. Exosomes in cancer diagnostics. Cancers (Basel). 2017;9(1):e8.CrossRef
63.
Greening DW, Gopal SK, Xu R, Simpson RJ, Chen W. Exosomes and their roles in immune regulation and cancer. Semin Cell Dev Biol. 2015;40:72–81.PubMedCrossRef
64.
65.
Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, et al. B lymphocytes secrete antigen-presenting vesicles. J Exp Med. 1996;183(3):1161–72.PubMedCrossRef
66.
Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, et al. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell derived exosomes. Nat Med. 1998;4(5):594–600.PubMedCrossRef
67.
Pitt JM, André F, Amigorena S, Soria JC, Eggermont A, Kroemer G, et al. Dendritic cell-derived exosomes for cancer therapy. J Clin Invest. 2016;126(4):1224–32.PubMedPubMedCentralCrossRef
68.
Segura E, Nicco C, Lombard B, Véron P, Raposo G, Batteux F, et al. ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming. Blood. 2005;106(1):216–23.PubMedCrossRef
69.
Clayton A, Court J, Navabi H, Adams M, Mason MD, Hobot JA, et al. Analysis of antigen presenting cell derived exosomes, based on immuno-magnetic isolation and flow cytometry. J Immunol Methods. 2001;247(1–2):163–74.PubMedCrossRef
70.
Théry C, Regnault A, Garin J, Wolfers J, Zitvogel L, Ricciardi-Castagnoli P, et al. Molecular characterization of dendritic cell-derived exosomes: selective accumulation of the heat shock protein hsc73. J Cell Biol. 1999;147(3):599–610.PubMedPubMedCentralCrossRef
71.
72.
Utsugi-Kobukai S, Fujimaki H, Hotta C, Nakazawa M, Minami M. MHC class I-mediated exogenous antigen presentation by exosomes secreted from immature and mature bone marrow derived dendritic cells. Immunol Lett. 2003;89(2):125–31.PubMedCrossRef
73.
Admyre C, Johansson SM, Paulie S, Gabrielsson S. Direct exosome stimulation of peripheral human T cells detected by ELISPOT. Eur J Immunol. 2006;36(7):1772–81.PubMedCrossRef
74.
Vincent-Schneider H, Stumptner-Cuvelette P, Lankar D, Pain S, Raposo G, Benaroch P, et al. Exosomes bearing HLA-DR1 molecules need dendritic cells to efficiently stimulate specific T cells. Int Immunol. 2002;14(7):713–22.PubMedCrossRef
75.
76.
Théry C, Duban L, Segura E, Véron P, Lantz O, Amigorena S. Indirect activation of naive CD4+ T cells by dendritic cell-derived exosomes. Nat Immunol. 2002;3(12):1156–62.PubMedCrossRef
77.
Segura E, Guerin C, Hogg N, Amigorena S, Thery C. CD8+ dendritic cells use LFA-1 to capture MHC-peptide complexes from exosomes in vivo. J Immunol. 2007;79(3):1489–96.CrossRef
78.
Montecalvo A, Shufesky WJ, Stolz DB, Sullivan MG, Wang Z, Divito SJ, et al. Exosomes as a short-range mechanism to spread alloantigen between dendritic cells during T cell allorecognition. J Immunol. 2008;180(5):3081–90.PubMedCrossRef
79.
Viaud S, Ploix S, Lapierre V, Théry C, Commere PH, Tramalloni D, et al. Updated technology to produce highly immunogenic dendritic cell-derived exosomes of clinical grade: a critical role of interferon-γ. J Immunol. 2011;34(1):65–75.
80.
Segura E, Amigorena SC. Mature dendritic cells secrete exosomes with strong ability to induce antigen-specific effector immune responses. Blood Cells Mol Dis. 2005;35(2):89–93.PubMedCrossRef
81.
Nakayama M. Antigen presentation by MHC-dressed cells. Front Immunol. 2014;5:672.PubMed
82.
Andre F, Schartz NE, Chaput N, Flament C, Raposo G, Amigorena S, et al. Tumor-derived exosomes: a new source of tumor rejection antigens. Vaccine. 2002;20(Suppl 4):A28–31.PubMedCrossRef
83.
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):247–54.PubMedCrossRef
84.
Ohno S, Drummen GP, Kuroda M. Focus on extracellular vesicles: development of extracellular vesicle-based therapeutic systems. Int J Mol Sci. 2016;17(2):172.PubMedPubMedCentralCrossRef
85.
Yang C, Kim SH, Bianco NR, Robbins PD. Tumor-derived exosomes confer antigen-specific immunosuppression in a murine delayed-type hypersensitivity model. PLoS One. 2011;6(8):e22517.PubMedPubMedCentralCrossRef
86.
Yang C, Ruffner MA, Kim SH, Robbins PD. Plasma-derived MHCII+ exosomes from tumor-bearing mice suppress tumor antigen-specific immune responses. Eur J Immunol. 2012;42(7):1778–84.PubMedPubMedCentralCrossRef
87.
Altieri SL, Khan AN, Tomasi TB. Exosomes from plasmacytoma cells as a tumor vaccine. J Immunother. 2004;27(4):282–8.PubMedCrossRef
88.
Mallegol J, Van NG, Lebreton C, Lepelletier Y, Candalh C, Dugave C, et al. T84-intestinal epithelial exosomes bear MHC class II/peptide complexes potentiating antigen presentation by dendritic cells. Gastroenterology. 2007;32(5):1866–76.CrossRef
89.
Viaud S, Théry C, Ploix S, Tursz T, Lapierre V, Lantz O, et al. Dendritic cell-derived exosomes for cancer immunotherapy: what’s next? Cancer Res. 2010;70(4):1281–5.PubMedCrossRef
90.
Hsu DH, Paz P, Villaflor G, Rivas A, Mehta-Damani A, Angevin E, et al. Exosomes as a tumor vaccine: enhancing potency through direct loading of antigenic peptides. J Immunother. 2003;26(5):440–5.PubMedCrossRef
91.
Chaput N, Flament C, Viaud S, Taieb J, Roux S, Spatz A, et al. Dendritic cell derived-exosomes: biology and clinical implementations. J Leukoc Biol. 2006;80(3):471–8.PubMedCrossRef
92.
Escudier B, Dorval T, Chaput N, André F, Caby MP, Novault S, et al. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of the first phase I clinical trial. J Trans Med. 2005;3(1):10.CrossRef
93.
Morse MA, Garst J, Osada T, Khan S, Hobeika A, Clay TM, et al. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J Transl Med. 2005;3(1):9.PubMedPubMedCentralCrossRef
94.
Besse B, Charrier M, Lapierre V, Dansin E, Lantz O, Planchard D, et al. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. Oncoimmunology. 2015;5(4):e1071008.PubMedPubMedCentralCrossRef
95.
96.
Dai S, Wei D, Wu Z, Zhou X, Wei X, Huang H, et al. Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer. Mol Ther. 2008;16(4):782–90.PubMedCrossRef
97.
98.
Yang Y, Xiu F, Cai Z, Wang J, Wang Q, Fu Y, et al. Increased induction of antitumor response by exosomes derived from interleukin-2 gene-modified tumor cells. J Clin Oncol. 2007;133(6):389–99.
99.
Wang J, Wang L, Lin Z, Tao L, Chen M. More efficient induction of antitumor T cell immunity by exosomes from CD40L gene-modified lung tumor cells. Mol Med Rep. 2014;9(1):125–31.PubMedCrossRef
100.
Chen W, Wang J, Shao C, Liu S, Yu Y, Wang Q, et al. Efficient induction of antitumor T cell immunity by exosomes derived from heat-shocked lymphoma cells. Eur J Immunol. 2010;36(6):1598–607.CrossRef
101.
Dai S, Zhou X, Wang B, Wang Q, Fu Y, Chen T, et al. Enhanced induction of dendritic cell maturation and HLA-A*0201-restricted CEA-specific CD8(+) CTL response by exosomes derived from IL-18 gene-modified CEA-positive tumor cells. J Mol Med. 2006;84(12):1067–76.PubMedCrossRef
102.
Chen T, Guo J, Yang M, Zhu X, Cao X. Chemokine-containing exosomes are released from heat-stressed tumor cells via lipid raft-dependent pathway and act as efficient tumor vaccine. J Immunol. 2011;186(4):2219–28.PubMedCrossRef
103.
Muller L, Muller-Haegele S, Mitsuhashi M, Gooding W, Okada H, Whiteside TL. Exosomes isolated from plasma of glioma patients enrolled in a vaccination trial reflect antitumor immune activity and might predict survival. Oncoimmunology. 2015;4(6):e1008347.PubMedPubMedCentralCrossRef
104.
105.
106.
Guo F, Chang CK, Fan HH, Nie XX, Ren YN, Liu YY, et al. Anti-tumour effects of exosomes in combination with cyclophosphamide and polyinosinic-polycytidylic acid. J Int Med Res. 2008;36(6):1342–53.PubMedCrossRef
Metadata
Title
The crosstalk between autophagic and endo-/exosomal pathways in antigen processing for MHC presentation in anticancer T cell immune responses
Authors
Liangshun You
Liping Mao
Juying Wei
Shenhe Jin
Chunmei Yang
Hui Liu
Li Zhu
Wenbin Qian
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2017
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/s13045-017-0534-8

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