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Regulation of Cancer Immune Checkpoints pp 431–453Cite as

Checkpoints Under Traffic Control: From and to Organelles

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1248))

Abstract

Immune checkpoints are variegated stimulatory and inhibitory signals that are fundamental in immune homeostasis. The regulative molecules for immune checkpoints include programmed cell death protein 1 (PD1), programmed death-ligand 1 or 2 (PD-L1 or PD-L2), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and so on. While the immune checkpoint molecules have gained soaring attention in recent years, the trafficking of them has been rarely studied. Since all of the discovered immune checkpoint molecules are transmembrane domain (TMD) proteins, they share similar pathophysiological characteristics which make studies about their trafficking and associated disorders resembled. PD-L1 is one of the most classic immune checkpoint molecules, and anti-PD1 monoantibodies have shown promising immunotherapeutic effects. PD-L1 trafficking has been particularly studied, the key regulators of which include metformin, chemokine-like factor-like MARVEL transmembrane domain-containing family member (CMTM), Huntingtin-interacting protein 1-related (HIP1R), exosomes, ALIX, polyI:C, and various post-translational modifications. Here, we focus on the checkpoints under traffic control, counting PD-L1, CTLA-4, lymphocyte-activation gene 3 (LAG-3), killer immunoglobulin-like receptors (KIRs), CD70, CD94, and attempt to shed light on the potentials of drug targets based on these findings and look forward to further studies in combinatorial therapeutic regimens in the meantime.

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References

  • Abd Elmageed ZY, Yang Y, Thomas R, Ranjan M, Mondal D, Moroz K et al (2014) Neoplastic reprogramming of patient-derived adipose stem cells by prostate cancer cell-associated exosomes. Stem Cells 32(4):983–997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aditi V et al (2016) TLR3-Induced maturation of murine dendritic cells regulates CTL responses by modulating PD-L1 trafficking. PLoS ONE 11(12):e0167057

    Article  CAS  Google Scholar 

  • Akbay EA et al (2013) Activation of the PD-1 pathway contributes to immune escape in EGFR-driven lung tumors. Cancer Discov 3(12):1355–1363

    Article  CAS  PubMed  Google Scholar 

  • Anjos S et al (2002) A common autoimmunity predisposing signal peptide variant of the cytotoxic T-lymphocyte antigen 4 results in inefficient glycosylation of the susceptibility allele. J Biol Chem 277(48):46478–46486

    Article  CAS  PubMed  Google Scholar 

  • Anna MK, Tom AG, Jannie B et al (2007) Costimulatory ligand CD70 is delivered to the immunological synapse by shared intracellular trafficking with MHC class II molecules. Proc Natl Acad Sci USA 104(14):5989–5994

    Article  CAS  Google Scholar 

  • Azuma K et al (2014) Association of PD-L1 overexpression with activating EGFR mutations in surgically resected nonsmall-cell lung cancer. Ann Oncol 25(10):1935–1940

    Article  CAS  PubMed  Google Scholar 

  • Bae J et al (2014) Trafficking of LAG-3 to the surface on activated T cells via its cytoplasmic domain and protein kinase C signaling. J Immunol 193(6):3101–3112

    Article  CAS  PubMed  Google Scholar 

  • Bauer PO et al (2010) Harnessing chaperone-mediated autophagy for the selective degradation of mutant huntingtin protein. Nat Biotechnol 28(3):256–263

    Article  CAS  PubMed  Google Scholar 

  • Becart S, Altman A (2009) SWAP-70-like adapter of T cells: a novel Lck-regulated guanine nucleotide exchange factor coordinating actin cytoskeleton reorganization and Ca2+ signaling in T cells. Immunol Rev 232(1):319–333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Becker A et al (2016) Extracellular vesicles in cancer: cell-to-cell mediators ofmetastasis. Cancer Cell 30(6):836–848

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biassoni R et al (1997) Role of amino acid position 70 in the binding affinity of p 50.1 and p58.1 receptors for HLA-Cw4 molecules. Eur J Immunol. 27(12):3095–3099

    Google Scholar 

  • Bissig C, Gruenberg J (2014) ALIX and the multivesicular endosome: ALIX in wonderland. Trends Cell Biol 24(1):19–25

    Article  CAS  PubMed  Google Scholar 

  • Bobrie A et al (2012) Rab27a supports exosome-dependent and -independent mechanisms that modify the tumor microenvironment and can promote tumor progression. Cancer Res 72(19):4920–4930

    Article  CAS  PubMed  Google Scholar 

  • Boes M, Meyer-Wentrup F (2015) TLR3 triggering regulates PD-L1 (CD274) expression in human neuroblastoma cells. Cancer Lett 361(1):49–56

    Article  CAS  PubMed  Google Scholar 

  • Bondeson DP et al (2015) Catalytic in vivo protein knockdown by small-molecule PROTACs. Nat Chem Biol 11(8):611–617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borel AC, Simon SM (1996) Biogenesis of polytopic membrane proteins: membrane segments assemble within translocation channels prior to insertion within the endoplasmic reticulum. Cell 85(3):379–389

    Article  CAS  PubMed  Google Scholar 

  • Borrego F, Masilamani M, Marusina AI, Tang X, Coligan JE (2006) The CD94/NKG2 family of receptors: from molecules and cells to clinical relevance. Immunol Res 35(3):263–278

    Article  CAS  PubMed  Google Scholar 

  • Boyce AM, Collins MT (1993) Fibrous dysplasia/MCCUNE-albright syndrome. In: Genereviews

    Google Scholar 

  • Breitling J, Aebi M (2013) N-linked protein glycosylation in the endoplasmic reticulum. Cold Spring Harb Perspect Biol 5(8):a013359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bunnett Nigel W, Cottrell Graeme S (2010) Trafficking and signaling of G protein-coupled receptors in the nervous system: implications for disease and therapy. CNS Neurol Disord Drug Targets 9(5):539–556

    Article  CAS  PubMed  Google Scholar 

  • Burgess SJ et al (2006) IL-21 down-regulates NKG2D/DAP10 expression on human NK and CD8+ T cells. J Immunol 176(3):1490–1497

    Article  CAS  PubMed  Google Scholar 

  • Burr Marian L et al (2017) CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity. Nature 549(7670):101–105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caporaso GL et al (1994) Morphologic and biochemical analysis of the intracellular trafficking of the Alzheimer beta/A4 amyloid precursor protein. J Neurosci 14(5 Pt 2):3122–3138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carlton J (2010) The ESCRT machinery: a cellular apparatus for sorting and scission. Biochem Soc Trans 38(6):1397–1412

    Article  CAS  PubMed  Google Scholar 

  • Caskey M et al (2011) Synthetic double-stranded RNA induces innate immune responses similar to a live viral vaccine in humans. J Exp Med 208(12):2357–2366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cha et al (2018) Metformin promotes antitumor immunity via endoplasmic-reticulum-associated degradation of PD-L1. Mol Cell 71(4):606–620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang CH, Flavell RA (1995) Class II transactivator regulates the expression of multiple genes involved in antigen presentation. J Exp Med 181(2):765–767

    Article  CAS  PubMed  Google Scholar 

  • Che TF et al (2015) Mitochondrial translocation of EGFR regulates mitochondria dynamics and promotes metastasis in NSCLC. Oncotarget 6(35):37349–37366

    Article  PubMed  PubMed Central  Google Scholar 

  • Chewning JH et al (2007) KIR2DS1-positive NK cells mediate alloresponse against the C2 HLA-KIR ligand group in vitro. J Immunol. 179(2):854–868

    Article  CAS  PubMed  Google Scholar 

  • Christian C, Screenivasan P (2003) Aberrant trafficking of transmembrane proteins in human disease. Trends Cell Biol 13(12):639–647

    Article  CAS  Google Scholar 

  • Chuang E et al (1997) Interaction of CTLA-4 with the clathrin-associated protein AP50 results in ligand-in-dependent endocytosis that limits cell surface expression. J Immunol 159(1):144–151

    CAS  PubMed  Google Scholar 

  • Chwae YJ et al (2007) Activation-induced upregulation of inhibitory killer Ig-like receptors is regulated by protein kinase C. Immunol Cell Biol 85(3):220–228

    Article  CAS  PubMed  Google Scholar 

  • Chwae YJ et al (2008) Amino-acid sequence motifs for PKC-mediated membrane trafficking of the inhibitory killer Ig-like receptor. Immunol Cell Biol 86(4):372–380

    Article  CAS  PubMed  Google Scholar 

  • Cocucci E, Racchetti G, Meldolesi J (2008) Shedding microvesicles: artefacts no more. Trends Cell Biol 19(2):43–51

    Article  CAS  Google Scholar 

  • Colonna M, Moretta A, Vély F, Vivier E (2000) A high-resolution view of NK-cell receptors: structure and function. Immunol Today 21(9):428–431

    Article  CAS  PubMed  Google Scholar 

  • Corrado C et al (2013) Exosomes as intercellular signaling organelles involved in health and disease: basic science and clinical applications. Int J Mol Sci 14(3):5338–5366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dal Bello MG et al (2017) Understanding the checkpoint blockade in lung cancer immunotherapy. Drug Discov Today 22(8):1266–1273

    Article  CAS  Google Scholar 

  • Daud AI, Hamid O, Ribas A, et al (2014) Antitumor activity of the anti-PD-1 monoclonal antibody MK-3475 in melanoma (MEL): Correlation of tumor PD-L1 expression with outcome. AACR Annual Meeting. CT104

    Google Scholar 

  • Danzer KM, Kranich LR, Ruf WP, Cagsal-Getkin O, Winslow AR, Zhu L et al (2012) Exosomal cell-to-cell transmission of alpha synuclein oligomers. Mol Neurodegener. 7:42

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dauer W, Przedborski S (2003) Parkinson’s disease: mechanisms and models. Neuron 39(6):889–909

    Article  CAS  PubMed  Google Scholar 

  • de la Cuesta-Zuluaga J, Mueller NT, Corrales-Agudelo V, Velásquez-Mejía EP, Carmona JA, Abad JM, Escobar JS (2017) Metformin is associated with higher relative abundance of mucin-degrading akkermansia muciniphila and several short-chain fatty acid-producing microbiota in the gut. Diabetes Care 40(1):54–62

    Article  CAS  PubMed  Google Scholar 

  • De Rham C et al (2007) The proinflammatory cytokines IL-2, IL-15 and IL-21 modulate the repertoire of mature human natural killer cell receptors. Arthritis Res Ther 9(6):R125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ding L et al (2015) Metformin prevents cancer metastasis by inhibiting M2-like polarization of tumor associated macrophages. Oncotarget 6(34):36441–36455

    Article  PubMed  PubMed Central  Google Scholar 

  • Eden ER et al (2012) The role of EGF receptor ubiquitination in regulating its intracellular traffic. Traffic 13(2):329–337

    Article  CAS  PubMed  Google Scholar 

  • Eikawa S, Nishida M, Mizukami S, Yamazaki C, Nakayama E, Udono H (2015) Immune-mediated antitumor effect by type 2 diabetes drug, metformin. Proc Natl Acad Sci USA 112(6):1809–1814

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Emanueli C, Shearn AI, Angelini GD, Sahoo S (2015) Exosomes and exosomal miRNAs in cardiovascular protection and repair. Vascul Pharmacol 71:24–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD (2005) Metformin and reduced risk of cancer in diabetic patients. BMJ 330(7503):1304–1305

    Article  PubMed  PubMed Central  Google Scholar 

  • Fan X et al (2014) Rapid and reversible knockdown of endogenous proteins by peptide-directed lysosomal degradation. Nat Neurosci 17(3):471–480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feng YH et al (2010) Sprouty2 protein enhances the response to gefitinib through epidermal growth factor receptor in colon cancer cells. Cancer Sci 101(9):2033–2038

    Article  CAS  PubMed  Google Scholar 

  • Ferris SP, Kodali VK, Kaufman RJ (2014) Glycoprotein folding and quality-control mechanisms in protein-folding diseases. Dis Model Mech 7(3):331–341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Forslund K, Hildebrand F, Nielsen T, Falony G, Le Chatelier E, Sunagawa S, Prifti E, Vieira-Silva S, Gudmundsdottir V, Pedersen HK et al (2015) Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature 528(7581):262–266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frame S, Cohen P (2001) GSK3 takes centre stage more than 20 years after its discovery. Biochem J 359(Pt 1):1–16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Freeman GJ, Long AJ, Iwai Y et al (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192(7):1027–1034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Friedl P, den Boer AT, Gunzer M (2005) Tuning immune responses: diversity and adaptation of the immunological synapse. Nat Rev Immunol 5(7):532–545

    Article  CAS  PubMed  Google Scholar 

  • Gandhi L, Balmanoukian A, Hui R et al (2014) MK-3475 (anti-PD-1 monoclonal antibody) for non-small cell lung cancer (NSCLC): antitumor activity and association with tumor PD-L1 expression. AACR Annual Meeting. CT105

    Google Scholar 

  • Gang C et al (2018) Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature 560(7718):382–386

    Article  CAS  Google Scholar 

  • Gargalionis AN et al (2014) The molecular rationale of Src inhibition in colorectal carcinomas. Int J Cancer 134(9):2019–2029

    Article  CAS  PubMed  Google Scholar 

  • Goodwin RG, Alderson MR, Smith CA, Armitage RJ, Vandenbos T, Jerzy R, Tough TW, Schoenborn M, Davies-Smith T, Hennen K et al (1993) Molecular and biological characterization of a ligand for CD27 defines a new family of cytokines with homology to tumor necrosis factor. Cell 73(3):447–456

    Article  CAS  PubMed  Google Scholar 

  • Gottfried I, Ehrlich M, Ashery U (2010) The Sla2p/HIP1/HIP1R family: similar structure, similar function in endocytosis? Biochem Soc Trans 38(Pt 1):187–191

    Article  CAS  PubMed  Google Scholar 

  • Greenberg M et al (1998) A dileucine motif in HIV-1 Nef is essential for sorting into clathrin-coated pits and for downregulation of CD4. Curr Biol 8(22):1239–1242

    Article  CAS  PubMed  Google Scholar 

  • Gumperz JE, Parham P (1995) The enigma of the natural killer cell. Nature 378(6554):245–248

    Article  CAS  PubMed  Google Scholar 

  • Gyorgy B et al (2011) Membrane vesicles current state-of-the-art: emerging role of extracellular vesicles. Cell Mol Life Sci 68(16):2667–2688

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haderk F et al (2017) Tumor-derived exosomes modulate PD-L1 expression in monocytes. Sci Immunol. 2(13):eaah5509

    Google Scholar 

  • Han W et al (2003) Identification of eight genes encoding chemokine-like factor superfamily members 1–8 (CKLFSF1–8) by in silico cloning and experimental validation. Genomics 81(6):609–617

    Article  CAS  PubMed  Google Scholar 

  • Hanyaloglu Aylin C, von Zastrow Mark (2008) Regulation of GPCRs by endocytic membrane trafficking and its potential implications. Ann Rev Pharmacol Toxicol 48:537–568

    Article  CAS  Google Scholar 

  • Henne WM et al (2011) The ESCRT pathway. Dev Cell 21(1):77–91

    Article  CAS  PubMed  Google Scholar 

  • Huanbing W et al (2018) HIP1R targets PD-L1 to lysosomal degradation to alter T-cell mediated cytotoxicity. Nat Chem Biol 15(1):42–50

    Google Scholar 

  • Huard B et al (1995) CD4/major histocompatibility complex class II interaction analyzed with CD4- and lymphocyte activation gene-3 (LAG-3)-Ig fusion proteins. Eur J Immunol 25(9):2718–2721

    Article  CAS  PubMed  Google Scholar 

  • Huard B et al (1997) Characterization of the major histocompatibility complex class II binding site on LAG-3 protein. Proc Natl Acad Sci USA 94(11):5744–5749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hurley JH (2015) ESCRTs are everywhere. EMBO J 34(19):2398–2407

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Iida T et al (2000) Regulation of cell surface expression of CTLA-4 by secretion of CTLA-4-containing lysosomes upon activation of CD4+ T cells. J Immunol 165(9):5062–5068

    Article  CAS  PubMed  Google Scholar 

  • Iwai Y, Ishida M, Tanaka Y et al (2002) Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA 99(19):12293–12297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jain RN et al (2008) Hip1r is expressed in gastric parietal cells and is required for tubulovesicle formation and cell survival in mice. J Clin Invest 118(7):2459–2470

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kalra H, Drummen GP, Mathivanan S (2016) Focus on extracellular vesicles: introducing the next small big thing. Int J Mol Sci 17(2):170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khailaie S et al (2018) Characterization of CTLA4 trafficking and implications for its function. Biophys J 115(7):1330–1343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kunisada Y et al (2017) Attenuation of CD4+ CD25+ regulatory T cells in the tumor microenvironment by metformin, a type 2 diabetes drug. EBioMedicine 25:154–164

    Article  PubMed  PubMed Central  Google Scholar 

  • Kyriachenko Y, Falalyeyeva T, Korotkyi O, Molochek N, Kobyliak N (2019) Crosstalk between gut microbiota and antidiabetic drug action. World J Diabetes 10(3):154–168

    Article  PubMed  PubMed Central  Google Scholar 

  • Kyttala A et al (2005) AP-1 and AP-3 facilitate lysosomal targeting of Batten disease protein CLN3 via its dileucine motif. J Biol Chem 280(11):10277–10283

    Article  CAS  PubMed  Google Scholar 

  • Lanier LL (1998) NK cell receptors. Ann Rev Immunol 16:359–393

    Article  CAS  Google Scholar 

  • Latchman Y, Wood CR, Chernova T et al (2001) PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat Immunol 2(3):261–268

    Article  CAS  PubMed  Google Scholar 

  • Laurence Z et al (2016) Immunological off-target effects of imatinib. Nat Rev Clin Oncol 13(7):431–446

    Article  CAS  Google Scholar 

  • Lee H, Lee Y, Kim J, An J, Lee S, Kong H, Song Y, Lee CK, Kim K (2018) Modulation of the gut microbiota by metformin improves metabolic profiles in aged obese mice. Gut Microbes 9(2):155–165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lemmon MA, Schlessinger J (2010) Cell signaling by receptor tyrosine kinases. Cell 141(7):1117–1134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leroyer AS, Isobe H, Leseche G, Castier Y, Wassef M, Mallat Z et al (2007) Cellular origins and thrombogenic activity of microparticles isolated from human atherosclerotic plaques. J Am Coll Cardiol 49(7):772–777

    Article  CAS  PubMed  Google Scholar 

  • Leung HT et al (1995) Cytotoxic T lymphocyte-associated molecule-4, a high avidity receptor for CD80 and CD86, contains an intracellular localization motif in its cytoplasmic tail. J Biol Chem 270(42):25107–25114

    Article  CAS  PubMed  Google Scholar 

  • Li N et al (2007) Metalloproteases regulate T-cell proliferation and effector function via LAG-3. EMBO J 26(2):494–504

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li J et al (2013) Exosomes mediate the cell-to-cell transmission of IFN-α-induced antiviral activity. Nat Immunol 14(8):793–803

    Article  CAS  PubMed  Google Scholar 

  • Li CW, Lim SO, Xia W, Lee HH, Chan LC, Kuo CW, Khoo KH, Chang SS, Cha JH, Kim T et al (2016) Glycosylation and stabilization of programmed death ligand-1 suppresses T-cell activity. Nat Commun 7:12632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li CW et al (2018) Eradication of triple-negative breast cancer cells by targeting glycosylated PD-L1. Cancer Cell 33(2):187–201.e10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lim SO et al (2016) Deubiquitination and stabilization of PD-L1 by CSN5. Cancer Cell 30(6):925–939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Linsley PS et al (1996) Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement. Immunity 4(6):535–543

    Article  CAS  PubMed  Google Scholar 

  • Lo B et al (2015) Patients with LRBA deficiency show CTLA4 loss and immune dysregulation responsive to abatacept therapy. Science 349(6246):436–440

    Article  CAS  PubMed  Google Scholar 

  • Madhan M, Sriram N, Martha P, Francisco B, John EC (2008) Uncommon endocytic and trafficking pathway of the natural killer cell CD94/NKG2A inhibitory receptor. Traffic 9(6):1019–1034

    Article  CAS  Google Scholar 

  • Marchese A, Benovic JL (2001) Agonist-promoted ubiquitination of the G protein-coupled receptor CXCR4 mediates lysosomal sorting. J Biol Chem 276(49):45509–45512

    Article  CAS  PubMed  Google Scholar 

  • Masyuk AI, Masyuk TV, Larusso NF (2013) Exosomes in the pathogenesis, diagnostics and therapeutics of liver diseases. J Hepatol 59(3):621–625

    Article  CAS  PubMed  Google Scholar 

  • Meacham GC et al (2001) The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation. Nat Cell Biol 3(1):100–105

    Article  CAS  PubMed  Google Scholar 

  • Mead KI et al (2005) Exocytosis of CTLA-4 is dependent on phospholipase D and ADP ribosylation factor-1 and stimulated during activation of regulatory T cells. J. Immunol 174(8):4803–4811

    Article  CAS  PubMed  Google Scholar 

  • Mendelsohn J, Baselga J (2006) Epidermal growth factor receptor targeting in cancer. Semin Oncol 33(4):369–385

    Article  CAS  PubMed  Google Scholar 

  • Monypenny et al (2018) ALIX regulates tumor-mediated immunosuppression by controlling EGFR activity and PD-L presentation. Cell Rep 24(3):630–641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moretta A et al (1996) Receptors for HLA class-I molecules in human natural killer cells. Ann Rev Immunol 14:619–648

    Article  CAS  Google Scholar 

  • Mulrooney TJ et al (2013) DAP12 impacts trafficking and surface stability of killer immunoglobulin-like receptors on natural killer cells. J Leukoc Biol 94(2):301–313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murillo MM et al (2014) RAS interaction with PI3K p110a is required for tumor-induced angiogenesis. J Clin Invest 124(8):3601–3611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nabet B et al (2018) The dTAG system for immediate and target-specific protein degradation. Nat Chem Biol 14(5):431–441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagato T, Lee YR, Harabuchi Y, Celis E (2014) Combinatorial immunotherapy of polyinosinic-polycytidylic acid and blockade of programmed death-ligand 1 induce effective CD8 T-cell responses against established tumors. Clin Cancer Res 20(5):1223–1234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oshima H, Nakano H, Nohara C, Kobata T, Nakajima A, Jenkins NA, Gilbert DJ, Copeland NG, Muto T, Yagita H, Okumura K (1998) Characterization of murine CD70 by molecular cloning and mAb. Int Immunol 10(4):517–526

    Article  CAS  PubMed  Google Scholar 

  • Ostrowski M et al (2010) Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 12(1):19–30

    Article  CAS  PubMed  Google Scholar 

  • Park YP et al (2011) Complex regulation of human NKG2D-DAP10 cell surface expression: opposing roles of the γc cytokines and TGF-β1. Blood 118(11):3019–3027

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pereira FV, Melo ACL, Low JS, de Castro ÍA, Braga TT, Almeida DC, Batista de Lima AGU, Hiyane MI, Correa-Costa M, Andrade-Oliveira V et al (2018) Metformin exerts antitumor activity via induction of multiple death pathways in tumor cells and activation of a protective immune response. Oncotarget 9(40):25808–25825

    Article  PubMed  PubMed Central  Google Scholar 

  • Pierre P, Turley SJ, Gatti E, Hull M, Meltzer J, Mirza A, Inaba K, Steinman R, Mellman I (1997) Developmental regulation of MHC class II transport in mouse dendritic cells. Nature 388(6644):787–792

    Article  CAS  PubMed  Google Scholar 

  • Poggio et al (2019) Suppression of exosomal PD-L1 induces systemic anti-tumor immunity and memory. Cell 177(2):414–427

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pollak M (2017) The effects of metformin on gut microbiota and the immune system as research frontiers. Diabetologia 60(9):1662–1667

    Article  CAS  PubMed  Google Scholar 

  • Pradere JP, Dapito DH, Schwabe RF (2014) The Yin and Yang of Toll-like receptors in cancer. Oncogene 33(27):3485–3495

    Article  CAS  PubMed  Google Scholar 

  • Pulko V et al (2009) TLR3-stimulated dendritic cells up-regulate B7-H1 expression and influence the magnitude of CD8 T cell responses to tumor vaccination. J Immunol 183(6):3634–3641

    Article  CAS  PubMed  Google Scholar 

  • Raiborg C, Stenmark H (2009) The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature 458(7237):445–452

    Article  CAS  PubMed  Google Scholar 

  • Rodig N, Ryan T, Allen JA et al (2003) Endothelial expression of PD-L1 and PD-L2 down-regulates CD8+ T cell activation and cytolysis. Eur J Immunol 33(11):3117–3126

    Article  CAS  PubMed  Google Scholar 

  • Roepstorff K et al (2009) Differential effects of EGFR ligands on endocytic sorting of the receptor. Traffic 10(8):1115–1127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rutishauser J, Spiess M (2002) Endoplasmic reticulum storage diseases. Swiss Med Wkly 132(17–18):211–222

    CAS  PubMed  Google Scholar 

  • Sakamoto KM et al (2001) Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation. Proc Natl Acad Sci USA 98(15):8554–8559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salmon H et al (2016) Expansion and activation of CD103(+) dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF inhibition. Immunity 44(4):924–938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanni TB, Masilamani M, Kabat J, Coligan JE, Borrego F (2004) Exclusion of lipid rafts and decreased mobility of CD94/NKG2A receptors at the inhibitory NK cell synapse. Mol Biol Cell 15(7):3210–3223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sansom DM (2000) CD28, CTLA-4 and their ligands: who does what and to whom? Immunology 101(2):169–177

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sansom DM (2015) Moving CTLA-4 from the trash to recycling. Science 349(6246):377–378

    Article  CAS  PubMed  Google Scholar 

  • Schneider H et al (1999) Cytolytic T lymphocyte-associated antigen-4 and the TCR zeta/CD3 complex, but not CD28, interact with clathrin adaptor complexes AP-1 and AP-2. J Immunol 163(4):1868–1879

    CAS  PubMed  Google Scholar 

  • Seiwert T, Burtness B, Weiss J et al (2014) A phase Ib study of MK-3475 in patients with human papillomavirus (HPV)-associated and non-HPV–associated head and neck (H/N) cancer. J Clin Oncol 32(15):6011–6011

    Article  Google Scholar 

  • Serwas Nina K et al (2019) Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis. Nat Commun 10(1):3106

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shin NR, Lee JC, Lee HY, Kim MS, Whon TW, Lee MS, Bae JW (2014) An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. Gut 63(5):727–735

    Google Scholar 

  • Shiratori T et al (1997) Tyrosine phosphorylation controls internalization of CTLA-4 by regulating its interaction with clathrin-associated adaptor complex AP-2. Immunity 6(5):583–589

    Article  CAS  PubMed  Google Scholar 

  • Snyder MR et al (2003) Selective activation of the c-Jun NH2-terminal protein kinase signaling pathway by stimulatory KIR in the absence of KARAP/DAP12 in CD4+ T cells. J Exp Med 197(4):437–449

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Snyder MR et al (2004) Stimulatory killer Ig-like receptors modulate T cell activation through DAP12-dependent and DAP12-independent mechanisms. J Immunol 173(6):3725–3731

    Article  CAS  PubMed  Google Scholar 

  • Steffens U et al (1998) Nucleotide and amino acid sequence alignment for human killer cell inhibitory receptors (KIR). Tissue Antigens 51(4 Pt 1):398–413

    CAS  PubMed  Google Scholar 

  • Stewart CA et al (2005) Recognition of peptide-MHC class I complexes by activating killer immunoglobulin-like receptors. Proc Natl Acad Sci USA 102(37):13224–13229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swanton E, Bulleid NJ (2003) Protein folding and translocation across the endoplasmic reticulum membrane. Mol Membr Biol 20(2):99–104

    Article  CAS  PubMed  Google Scholar 

  • Tan Xiaojun et al (2016) Stress-Induced EGFR trafficking: mechanisms, functions, and therapeutic implications. Trends Cell Biol 26(5):352–366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tesselaar K, Gravestein LA, van Schijndel GMW, Borst J, van Lier RAW (1997) Characterization of murine CD70, the ligand of the TNF receptor family member CD27. J Immunol 159(10):4959–4965

    CAS  PubMed  Google Scholar 

  • Triebel F et al (1990) LAG-3, a novel lymphocyte activation gene closely related to CD4. J Exp Med 171(5):1393–1405

    Article  CAS  PubMed  Google Scholar 

  • Turley SJ, Inaba K, Garrett WS, Ebersold M, Unternaehrer J, Steinman RM, Mellman I (2000) Transport of peptide-MHC class II complexes in developing dendritic cells. Science 288(5465):522–527

    Article  CAS  PubMed  Google Scholar 

  • Valk E et al (2006) T cell receptor-interacting molecule acts as a chaperone to modulate surface expression of the CTLA-4 coreceptor. Immunity 25(5):807–821

    Article  CAS  PubMed  Google Scholar 

  • Van der Pol E, Böing AN, Harrison P, Sturk A, Nieuwland R (2012) Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev 64(3):676–705

    Article  CAS  PubMed  Google Scholar 

  • Verdura S, Cuyàs E, Martin-Castillo B, Menendez JA (2019) Metformin as an archetype immuno-metabolic adjuvant for cancer immunotherapy. OncoImmunology 8(10). https://doi.org/10.1080/2162402x.2019.1633235

  • Walsh Alice M, Lazzara Matthew J (2013) Regulation of EGFR trafficking and cell signaling by Sprouty2 and MIG6 in lung cancer cells. J Cell Sci 126(Pt 19):4339–4348

    Article  CAS  PubMed  Google Scholar 

  • Woo SR et al (2010) Differential subcellular localization of the regulatory T-cell protein LAG-3 and the coreceptor CD4. Eur J Immunol 40(6):1768–1777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu H, Esteve E, Tremaroli V, Khan MT, Caesar R, Mannerås-Holm L, Ståhlman M, Olsson LM, Serino M, Planas-Fèlix M et al (2017) Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. Nat Med 23(7):850–858

    Article  CAS  PubMed  Google Scholar 

  • Wubbolts R, Fernandez-Borja M, Jordens I, Reits E, Dusseljee S, Echeverri C, Vallee RB, Neefjes J (1999) Opposing motor activities of dynein and kinesin determine retention and transport of MHC class II-containing compartments. J Cell Sci 112(Pt 6):785–795

    CAS  PubMed  Google Scholar 

  • Xu C, Ng DT (2015) Glycosylation-directed quality control of protein folding. Nat Rev Mol Cell Biol 16(12):742–752

    Article  CAS  PubMed  Google Scholar 

  • Yang Y et al (2019) Palmitoylation stabilizes PD-L1 to promote breast tumor growth. Cell Res 29(1):83–86

    Article  PubMed  Google Scholar 

  • Yao H et al (2019) Inhibiting PD-L1 palmitoylation enhances T-cell immune responses against tumours. Nat Biomed Eng 3(4):306–317

    Article  CAS  PubMed  Google Scholar 

  • Yi Y et al (2018) Exosomal PD-L1 harbors active defense function to suppress T cell killing of breast cancer cells and promote tumor growth. Cell Res 28(8):862–864

    Article  CAS  Google Scholar 

  • Zaborowski MP, Balaj L, Breakefield XO, Lai CP (2015) Extracellular vesicles: composition, biological relevance, and methods of study. Bioscience 65(8):783–797

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Allison JP (1997) Interaction of CTLA-4 with AP50, a clathrin-coated pit adaptor protein. Proc Natl Acad Sci USA 94(17):9273–9278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang X, Yuan X, Shi H, Wu L, Qian H, Xu W (2015) Exosomes in cancer: small particle, big player. J Hematol Oncol 8:83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang J et al (2018) Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature 553(7686):91–95

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Shouyan Deng

  2. Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China

    Xiaolin Zhou

  3. Institutes of Biomedical Sciences, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, 200032, China

    Jie Xu

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  1. Shouyan Deng
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  2. Xiaolin Zhou
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  3. Jie Xu
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Correspondence to Shouyan Deng .

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  1. Institutes of Biomedical Sciences, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China

    Jie Xu

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Deng, S., Zhou, X., Xu, J. (2020). Checkpoints Under Traffic Control: From and to Organelles. In: Xu, J. (eds) Regulation of Cancer Immune Checkpoints. Advances in Experimental Medicine and Biology, vol 1248. Springer, Singapore. https://doi.org/10.1007/978-981-15-3266-5_18

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