Abstract
We innately have an ability to reject tumors, thereby limiting cancer progression and metastasis. The major effector lymphocytes in tumor rejection are natural killer (NK) cells. NK cells kill target cancer cells by two different rejection mechanisms, NK receptor-dependent killing and tumor-necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated killing. In spite of these tumor rejection systems, cancer cells make survival in host, facilitating the metastatic spread to other organs. The metastatic spread is still the major cause of cancer deaths. It has been revealed that some cancer cells acquire an ability to evade tumor rejection responses by NK cells to survive longer in host, thereby increasing the chance to metastasize. Several immune evasion strategies have been well documented. Recently, the immune evasion mechanisms from NK immunity using cell-surface glycans have been identified. The cancer cells use the certain types of cell-surface glycans to evade NK immunity in the following three ways: reducing NK activating receptor-mediated signaling, enhancing NK inhibitory receptor-mediated signaling, and modulating TRAIL-mediated killing. In this chapter, we will illustrate those evasion mechanisms in which cell-surface glycans play a central role.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Notes
- 1.
Mucin-type O-glycan is a general term for the oligosaccharides which are initially found in cell-surface and secreted mucins. Those oligosaccharides contain the linkage of N-acetylgalactosamine (GalNAc) to serine or threonine residues. Mucin-type O-glycans are present on other cell-surface glycoproteins such as CD43 and CD34. In this chapter, we focus on the mucin-type O-glycans among O-glycans.
References
Clayton A, Mitchell JP, Court J, Linnane S, Mason MD, Tabi Z (2008) Human tumor-derived exosomes down-modulate NKG2D expression. J Immunol 180:7249–7258
Doubrovina ES, Doubrovin MM, Vider E, Sisson RB, O’Reilly RJ, Dupont B et al (2003) Evasion from NK cell immunity by MHC class I chain-related molecules expressing colon adenocarcinoma. J Immunol 171:6891–6899
Falschlehner C, Schaefer U, Walczak H (2009) Following TRAIL’s path in the immune system. Immunology 127:145–154
Fuertes MB, Girart MV, Molinero LL, Domaica CI, Rossi LE, Barrio MM et al (2008) Intracellular retention of the NKG2D ligand MHC class I chain-related gene A in human melanomas confers immune privilege and prevents NK cell-mediated cytotoxicity. J Immunol 180:4606–4614
Fukuda M (1996) Possible roles of tumor-associated carbohydrate antigens. Cancer Res 56:2237–2244
Fuster MM, Esko JD (2005) The sweet and sour of cancer: glycans as novel therapeutic targets. Nat Rev Cancer 5:526–542
Groh V, Wu J, Yee C, Spies T (2002) Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation. Nature 419:734–738
Guerra N, Tan YX, Joncker NT, Choy A, Gallardo F, Xiong N et al (2008) NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy. Immunity 28:571–580
Hagisawa S, Ohyama C, Takahashi T, Endoh M, Moriya T, Nakayama J et al (2005) Expression of core 2 beta1,6-N-acetylglucosaminyltransferase facilitates prostate cancer progression. Glycobiology 15:1016–1024
Hatakeyama S, Kyan A, Yamamoto H, Okamoto A, Sugiyama N, Suzuki Y et al (2010) Core 2 N-acetylglucosaminyltransferase expression induces aggressive potential of testicular germ cell tumor. Int J Cancer 127:1052–1059
Hudak JE, Canham SM, Bertozzi CR (2014) Glycocalyx engineering reveals a Siglec-based mechanism for NK cell immunoevasion. Nat Chem Biol 10:69–75
Joncker NT, Raulet DH (2008) Regulation of NK cell responsiveness to achieve self-tolerance and maximal responses to diseased target cells. Immunol Rev 224:85–97
Lanier LL (2008) Up on the tightrope: natural killer cell activation and inhibition. Nat Immunol 9:495–502
Leivonen M, Nordling S, Lundin J, von Boguslawski K, Haglund C (2001) STn and prognosis in breast cancer. Oncology 61:299–305
Levy EM, Roberti MP, Mordoh J (2011) Natural killer cells in human cancer: from biological functions to clinical applications. J Biomed Biotechnol 2011:676198
Machida E, Nakayama J, Amano J, Fukuda M (2001) Clinicopathological significance of core 2 beta1,6-N-acetylglucosaminyltransferase messenger RNA expressed in the pulmonary adenocarcinoma determined by in situ hybridization. Cancer Res 61:2226–2231
Mamessier E, Sylvain A, Thibult ML, Houvenaeghel G, Jacquemier J, Castellano R et al (2011) Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity. J Clin Invest 121:3609–3622
Miyoshi E, Moriwaki K, Nakagawa T (2008) Biological function of fucosylation in cancer biology. J Biochem 143:725–729
Moretta L, Bottino C, Pende D, Vitale M, Mingari MC, Moretta A (2004) Different checkpoints in human NK-cell activation. Trends Immunol 25:670–676
Moriwaki K, Noda K, Furukawa Y, Ohshima K, Uchiyama A, Nakagawa T et al (2009) Deficiency of GMDS leads to escape from NK cell-mediated tumor surveillance through modulation of TRAIL signaling. Gastroenterology 137:188–198, 98 e1-2
Nausch N, Cerwenka A (2008) NKG2D ligands in tumor immunity. Oncogene 27:5944–5958
Ogata S, Maimonis PJ, Itzkowitz SH (1992) Mucins bearing the cancer-associated sialosyl-Tn antigen mediate inhibition of natural killer cell cytotoxicity. Cancer Res 52:4741–4746
Ohyama C, Smith PL, Angata K, Fukuda MN, Lowe JB, Fukuda M (1998) Molecular cloning and expression of GDP-D-mannose-4,6-dehydratase, a key enzyme for fucose metabolism defective in Lec13 cells. J Biol Chem 273:14582–14587
Okamoto T, Yoneyama MS, Hatakeyama S, Mori K, Yamamoto H, Koie T et al (2013) Core2 O-glycan-expressing prostate cancer cells are resistant to NK cell immunity. Mol Med Rep 7:359–364
Oppenheim DE, Roberts SJ, Clarke SL, Filler R, Lewis JM, Tigelaar RE et al (2005) Sustained localized expression of ligand for the activating NKG2D receptor impairs natural cytotoxicity in vivo and reduces tumor immunosurveillance. Nat Immunol 6:928–937
Purdy AK, Campbell KS (2009) Natural killer cells and cancer: regulation by the killer cell Ig-like receptors (KIR). Cancer Biol Ther 8:2211–2220
Rabinovich GA, Rubinstein N, Fainboim L (2002) Unlocking the secrets of galectins: a challenge at the frontier of glyco-immunology. J Leukoc Biol 71:741–752
Raulet DH, Gasser S, Gowen BG, Deng W, Jung H (2013) Regulation of ligands for the NKG2D activating receptor. Annu Rev Immunol 31:413–441
Saegusa J, Hsu DK, Chen HY, Yu L, Fermin A, Fung MA et al (2009) Galectin-3 is critical for the development of the allergic inflammatory response in a mouse model of atopic dermatitis. Am J Pathol 174:922–931
Sullivan FX, Kumar R, Kriz R, Stahl M, Xu GY, Rouse J et al (1998) Molecular cloning of human GDP-mannose 4,6-dehydratase and reconstitution of GDP-fucose biosynthesis in vitro. J Biol Chem 273:8193–8202
Suzuki Y, Sutoh M, Hatakeyama S, Mori K, Yamamoto H, Koie T et al (2012) MUC1 carrying core 2 O-glycans functions as a molecular shield against NK cell attack, promoting bladder tumor metastasis. Int J Oncol 40:1831–1838
Trinchieri G (1989) Biology of natural killer cells. Adv Immunol 47:187–376
Tsuboi S (2013) Immunosuppressive functions of core2 O-glycans against NK immunity. Trends Glycosci Glycotechnol 25:117–123
Tsuboi S, Sutoh M, Hatakeyama S, Hiraoka N, Habuchi T, Horikawa Y et al (2011) A novel strategy for evasion of NK cell immunity by tumours expressing core2 O-glycans. EMBO J 30:3173–3185
Tsuboi S, Hatakeyama S, Ohyama C, Fukuda M (2012) Two opposing roles of O-glycans in tumor metastasis. Trends Mol Med 18:224–232
Valastyan S, Weinberg RA (2011) Tumor metastasis: molecular insights and evolving paradigms. Cell 147:275–292
Van Rinsum J, Smets LA, Van Rooy H, Van den Eijnden DH (1986) Specific inhibition of human natural killer cell-mediated cytotoxicity by sialic acid and sialo-oligosaccharides. Int J Cancer 38:915–922
Vivier E, Tomasello E, Baratin M, Walzer T, Ugolini S (2008) Functions of natural killer cells. Nat Immunol 9:503–510
Wagner KW, Punnoose EA, Januario T, Lawrence DA, Pitti RM, Lancaster K et al (2007) Death-receptor O-glycosylation controls tumor-cell sensitivity to the proapoptotic ligand Apo2L/TRAIL. Nat Med 13:1070–1077
Yang RY, Rabinovich GA, Liu FT (2008) Galectins: structure, function and therapeutic potential. Expert Rev Mol Med 10:e17
Zafirova B, Mandaric S, Antulov R, Krmpotic A, Jonsson H, Yokoyama WM et al (2009) Altered NK cell development and enhanced NK cell-mediated resistance to mouse cytomegalovirus in NKG2D-deficient mice. Immunity 31:270–282
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Japan
About this chapter
Cite this chapter
Tsuboi, S. (2015). Roles of Glycans in Immune Evasion from NK Immunity. In: Suzuki, T., Ohtsubo, K., Taniguchi, N. (eds) Sugar Chains. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55381-6_11
Download citation
DOI: https://doi.org/10.1007/978-4-431-55381-6_11
Published:
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-55380-9
Online ISBN: 978-4-431-55381-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)