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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2021 | Polio Virus | Review

Poliovirus receptor (PVR)-like protein cosignaling network: new opportunities for cancer immunotherapy

Authors: Baokang Wu, Chongli Zhong, Qi Lang, Zhiyun Liang, Yizhou Zhang, Xin Zhao, Yang Yu, Heming Zhang, Feng Xu, Yu Tian

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2021

Abstract

Immune checkpoint molecules, also known as cosignaling molecules, are pivotal cell-surface molecules that control immune cell responses by either promoting (costimulatory molecules) or inhibiting (coinhibitory molecules) a signal. These molecules have been studied for many years. The application of immune checkpoint drugs in the clinic provides hope for cancer patients. Recently, the poliovirus receptor (PVR)-like protein cosignaling network, which involves several immune checkpoint receptors, i.e., DNAM-1 (DNAX accessory molecule-1, CD226), TIGIT (T-cell immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM)), CD96 (T cell activation, increased late expression (TACLILE)), and CD112R (PVRIG), which interact with their ligands CD155 (PVR/Necl-5), CD112 (PVRL2/nectin-2), CD111 (PVRL1/nectin-1), CD113 (PVRL3/nectin-3), and Nectin4, was discovered. As important components of the immune system, natural killer (NK) and T cells play a vital role in eliminating and killing foreign pathogens and abnormal cells in the body. Recently, increasing evidence has suggested that this novel cosignaling network axis costimulates and coinhibits NK and T cell activation to eliminate cancer cells after engaging with ligands, and this activity may be effectively targeted for cancer immunotherapy. In this article, we review recent advances in research on this novel cosignaling network. We also briefly outline the structure of this cosignaling network, the signaling cascades and mechanisms involved after receptors engage with ligands, and how this novel cosignaling network costimulates and coinhibits NK cell and T cell activation for cancer immunotherapy. Additionally, this review comprehensively summarizes the application of this new network in preclinical trials and clinical trials. This review provides a new immunotherapeutic strategy for cancer treatment.

Zhu Y, Yao S, Chen L. Cell surface signaling molecules in the control of immune responses: a tide model. Immunity. 2011;34(4):466–78. https://doi.org/10.1016/j.immuni.2011.04.008.CrossRefPubMedPubMedCentral

Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 2013;13(4):227–42. https://doi.org/10.1038/nri3405.CrossRefPubMedPubMedCentral

Zang X, Allison JP. The B7 family and cancer therapy: costimulation and coinhibition. Clin Cancer Res. 2007;13(18):5271–9. https://doi.org/10.1158/1078-0432.CCR-07-1030.CrossRefPubMed

Gimmi CD, Freeman GJ, Gribben JG, Sugita K, Freedman AS, Morimoto C, et al. B-cell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2. Proc Natl Acad Sci U S A. 1991;88(15):6575–9. https://doi.org/10.1073/pnas.88.15.6575.CrossRefPubMedPubMedCentral

Harding FA, McArthur JG, Gross JA, Raulet DH, Allison JP. CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones. Nature. 1992;356(6370):607–9. https://doi.org/10.1038/356607a0.CrossRefPubMed

Koulova L, Clark EA, Shu G, Dupont B. The CD28 ligand B7/BB1 provides costimulatory signal for alloactivation of CD4+ T cells. J Exp Med. 1991;173(3):759–62. https://doi.org/10.1084/jem.173.3.759.CrossRefPubMed

Rudd CE, Taylor A, Schneider H. CD28 and CTLA-4 coreceptor expression and signal transduction. Immunol Rev. 2009;229(1):12–26. https://doi.org/10.1111/j.1600-065X.2009.00770.x.CrossRefPubMedPubMedCentral

Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34. https://doi.org/10.1084/jem.192.7.1027.CrossRefPubMedPubMedCentral

Lanier LL. Up on the tightrope: natural killer cell activation and inhibition. Nat Immunol. 2008;9(5):495–502. https://doi.org/10.1038/ni1581.CrossRefPubMedPubMedCentral

10.

Chodon T, Koya RC, Odunsi K. Active immunotherapy of Cancer. Immunol Investig. 2015;44(8):817–36. https://doi.org/10.3109/08820139.2015.1096684.CrossRef

11.

Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54. https://doi.org/10.1056/NEJMoa1200690.CrossRefPubMedPubMedCentral

12.

Shibuya A, Campbell D, Hannum C, Yssel H, Franz-Bacon K, McClanahan T, et al. DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity. 1996;4(6):573–81. https://doi.org/10.1016/S1074-7613(00)70060-4.CrossRefPubMed

13.

Zhang Z, Wu N, Lu Y, Davidson D, Colonna M, Veillette A. DNAM-1 controls NK cell activation via an ITT-like motif. J Exp Med. 2015;212(12):2165–82. https://doi.org/10.1084/jem.20150792.CrossRefPubMedPubMedCentral

14.

Bottino C, Castriconi R, Pende D, Rivera P, Nanni M, Carnemolla B, et al. Identification of PVR (CD155) and Nectin-2 (CD112) as cell surface ligands for the human DNAM-1 (CD226) activating molecule. J Exp Med. 2003;198(4):557–67. https://doi.org/10.1084/jem.20030788.CrossRefPubMedPubMedCentral

15.

Pende D, Bottino C, Castriconi R, Cantoni C, Marcenaro S, Rivera P, et al. PVR (CD155) and Nectin-2 (CD112) as ligands of the human DNAM-1 (CD226) activating receptor: involvement in tumor cell lysis. Mol Immunol. 2005;42(4):463–9. https://doi.org/10.1016/j.molimm.2004.07.028.CrossRefPubMed

16.

Shibuya A, Lanier LL, Phillips JH. Protein kinase C is involved in the regulation of both signaling and adhesion mediated by DNAX accessory molecule-1 receptor. J Immunol. 1998;161:1671–6.PubMed

17.

Ralston KJ, Hird SL, Zhang X, Scott JL, Jin B, Thorne RF, et al. The LFA-1-associated molecule PTA-1 (CD226) on T cells forms a dynamic molecular complex with protein 4.1G and human discs large. J Biol Chem. 2004;279(32):33816–28. https://doi.org/10.1074/jbc.M401040200.CrossRefPubMed

18.

Enqvist M, Ask EH, Forslund E, Carlsten M, Abrahamsen G, Béziat V, et al. Coordinated expression of DNAM-1 and LFA-1 in educated NK cells. J Immunol. 2015;194(9):4518–27. https://doi.org/10.4049/jimmunol.1401972.CrossRefPubMed

19.

Shibuya K, Shirakawa J, Kameyama T, Honda S, Tahara-Hanaoka S, Miyamoto A, et al. CD226 (DNAM-1) is involved in lymphocyte function-associated antigen 1 costimulatory signal for naive T cell differentiation and proliferation. J Exp Med. 2003;198(12):1829–39. https://doi.org/10.1084/jem.20030958.CrossRefPubMedPubMedCentral

20.

Kim HS, Das A, Gross CC, Bryceson YT, Long EO. Synergistic signals for natural cytotoxicity are required to overcome inhibition by c-Cbl ubiquitin ligase. Immunity. 2010;32(2):175–86. https://doi.org/10.1016/j.immuni.2010.02.004.CrossRefPubMedPubMedCentral

21.

Kim HS, Long EO. Complementary phosphorylation sites in the adaptor protein SLP-76 promote synergistic activation of natural killer cells. Sci Signal. 2012;5:ra49.PubMed

22.

Deng Y, Kerdiles Y, Chu J, Yuan S, Wang Y, Chen X, et al. Transcription factor Foxo1 is a negative regulator of natural killer cell maturation and function. Immunity. 2015;42(3):457–70. https://doi.org/10.1016/j.immuni.2015.02.006.CrossRefPubMedPubMedCentral

23.

Du X, de Almeida P, Manieri N, de Almeida ND, Wu TD, Harden Bowles K, et al. CD226 regulates natural killer cell antitumor responses via phosphorylation-mediated inactivation of transcription factor FOXO1. Proc Natl Acad Sci U S A. 2018;115(50):E11731–e11740. https://doi.org/10.1073/pnas.1814052115.CrossRefPubMedPubMedCentral

24.

Fourcade J, Sun Z, Chauvin JM, Ka M, Davar D, Pagliano O, et al. CD226 opposes TIGIT to disrupt Tregs in melanoma. JCI Insight. 2018;3(14). https://doi.org/10.1172/jci.insight.121157.

25.

Fuhrman CA, Yeh WI, Seay HR, Saikumar Lakshmi P, Chopra G, Zhang L, et al. Divergent phenotypes of human regulatory T cells expressing the receptors TIGIT and CD226. J Immunol. 2015;195(1):145–55. https://doi.org/10.4049/jimmunol.1402381.CrossRefPubMed

26.

Castriconi R, Dondero A, Corrias MV, Lanino E, Pende D, Moretta L, et al. Natural killer cell-mediated killing of freshly isolated neuroblastoma cells: critical role of DNAX accessory molecule-1-poliovirus receptor interaction. Cancer Res. 2004;64(24):9180–4. https://doi.org/10.1158/0008-5472.CAN-04-2682.CrossRefPubMed

27.

Gong J, Liu R, Zhuang R, Zhang Y, Fang L, Xu Z, et al. miR-30c-1* promotes natural killer cell cytotoxicity against human hepatoma cells by targeting the transcription factor HMBOX1. Cancer Sci. 2012;103(4):645–52. https://doi.org/10.1111/j.1349-7006.2012.02207.x.CrossRefPubMedPubMedCentral

28.

Ott M, Avendaño-Guzmán E, Ullrich E, Dreyer C, Strauss J, Harden M, et al. Laquinimod, a prototypic quinoline-3-carboxamide and aryl hydrocarbon receptor agonist, utilizes a CD155-mediated natural killer/dendritic cell interaction to suppress CNS autoimmunity. J Neuroinflammation. 2019;16(1):49. https://doi.org/10.1186/s12974-019-1437-0.CrossRefPubMedPubMedCentral

29.

Liu T, Zhang D, Zhang Y, Xu X, Zhou B, Fang L, et al. Blocking CD226 promotes allogeneic transplant immune tolerance and improves skin graft survival by increasing the frequency of regulatory T cells in a murine model. Cell Physiol Biochem. 2018;45(6):2338–50. https://doi.org/10.1159/000488182.CrossRefPubMed

30.

Toutirais O, Cabillic F, Le Friec G, Salot S, Loyer P, Le Gallo M, et al. DNAX accessory molecule-1 (CD226) promotes human hepatocellular carcinoma cell lysis by Vgamma9Vdelta2 T cells. Eur J Immunol. 2009;39(5):1361–8. https://doi.org/10.1002/eji.200838409.CrossRefPubMed

31.

Jin HS, Ko M, Choi DS, Kim JH, Lee DH, Kang SH, et al. CD226(hi)CD8(+) T cells are a prerequisite for anti-TIGIT immunotherapy. Cancer Immunol Res. 2020;8(7):912–25. https://doi.org/10.1158/2326-6066.CIR-19-0877.CrossRefPubMed

32.

Zhang Q, Bi J, Zheng X, Chen Y, Wang H, Wu W, et al. Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity. Nat Immunol. 2018;19(7):723–32. https://doi.org/10.1038/s41590-018-0132-0.CrossRefPubMed

33.

Maas RJ, Hoogstad-van Evert JS, Van der Meer JM, Mekers V, Rezaeifard S, Korman AJ, et al. TIGIT blockade enhances functionality of peritoneal NK cells with altered expression of DNAM-1/TIGIT/CD96 checkpoint molecules in ovarian cancer. Oncoimmunology. 2020;9(1):1843247. https://doi.org/10.1080/2162402X.2020.1843247.CrossRefPubMedPubMedCentral

34.

Chauvin JM, Pagliano O, Fourcade J, Sun Z, Wang H, Sander C, et al. TIGIT and PD-1 impair tumor antigen-specific CD8⁺ T cells in melanoma patients. J Clin Invest. 2015;125(5):2046–58. https://doi.org/10.1172/JCI80445.CrossRefPubMedPubMedCentral

35.

He W, Zhang H, Han F, Chen X, Lin R, Wang W, et al. CD155T/TIGIT signaling regulates CD8(+) T-cell metabolism and promotes tumor progression in human gastric Cancer. Cancer Res. 2017;77(22):6375–88. https://doi.org/10.1158/0008-5472.CAN-17-0381.CrossRefPubMed

36.

Guillerey C, Harjunpää H, Carrié N, Kassem S, Teo T, Miles K, et al. TIGIT immune checkpoint blockade restores CD8(+) T-cell immunity against multiple myeloma. Blood. 2018;132(16):1689–94. https://doi.org/10.1182/blood-2018-01-825265.CrossRefPubMed

37.

Minnie SA, Kuns RD, Gartlan KH, Zhang P, Wilkinson AN, Samson L, et al. Myeloma escape after stem cell transplantation is a consequence of T-cell exhaustion and is prevented by TIGIT blockade. Blood. 2018;132(16):1675–88. https://doi.org/10.1182/blood-2018-01-825240.CrossRefPubMed

38.

Wu L, Mao L, Liu JF, Chen L, Yu GT, Yang LL, et al. Blockade of TIGIT/CD155 signaling reverses T-cell exhaustion and enhances antitumor capability in head and neck squamous cell carcinoma. Cancer Immunol Res. 2019;7(10):1700–13. https://doi.org/10.1158/2326-6066.CIR-18-0725.CrossRefPubMed

39.

Lozano E, Mena MP, Díaz T, Martin-Antonio B, León S, Rodríguez-Lobato LG, et al. Nectin-2 expression on malignant plasma cells is associated with better response to TIGIT blockade in multiple myeloma. Clin Cancer Res. 2020;26(17):4688–98. https://doi.org/10.1158/1078-0432.CCR-19-3673.CrossRefPubMed

40.

Preillon J, Cuende J, Rabolli V, Garnero L, Mercier M, Wald N, et al. Restoration of T-cell effector function, depletion of Tregs, and direct killing of tumor cells: the multiple mechanisms of action of a-TIGIT antagonist antibodies. Mol Cancer Ther. 2021;20(1):121–31. https://doi.org/10.1158/1535-7163.MCT-20-0464.CrossRefPubMed

41.

Hung AL, Maxwell R, Theodros D, Belcaid Z, Mathios D, Luksik AS, et al. TIGIT and PD-1 dual checkpoint blockade enhances antitumor immunity and survival in GBM. Oncoimmunology. 2018;7:e1466769.CrossRef

42.

Chen F, Xu Y, Chen Y, Shan S. TIGIT enhances CD4(+) regulatory T-cell response and mediates immune suppression in a murine ovarian cancer model. Cancer Med. 2020;9(10):3584–91. https://doi.org/10.1002/cam4.2976.CrossRefPubMedPubMedCentral

43.

Blake SJ, Stannard K, Liu J, Allen S, Yong MC, Mittal D, et al. Suppression of metastases using a new lymphocyte checkpoint target for Cancer immunotherapy. Cancer Discov. 2016;6(4):446–59. https://doi.org/10.1158/2159-8290.CD-15-0944.CrossRefPubMed

44.

Sun H, Huang Q, Huang M, Wen H, Lin R, Zheng M, et al. Human CD96 correlates to natural killer cell exhaustion and predicts the prognosis of human hepatocellular carcinoma. Hepatology. 2019;70(1):168–83. https://doi.org/10.1002/hep.30347.CrossRefPubMed

45.

Roman Aguilera A, Lutzky VP, Mittal D, Li XY, Stannard K, Takeda K, et al. CD96 targeted antibodies need not block CD96-CD155 interactions to promote NK cell anti-metastatic activity. Oncoimmunology. 2018;7(5):e1424677. https://doi.org/10.1080/2162402X.2018.1424677.CrossRefPubMedPubMedCentral

46.

Chiang EY, de Almeida PE, de Almeida Nagata DE, Bowles KH, Du X, Chitre AS, et al. CD96 functions as a co-stimulatory receptor to enhance CD8(+) T cell activation and effector responses. Eur J Immunol. 2020;50(6):891–902. https://doi.org/10.1002/eji.201948405.CrossRefPubMed

47.

Mittal D, Lepletier A, Madore J, Aguilera AR, Stannard K, Blake SJ, et al. CD96 is an immune checkpoint that regulates CD8(+) T-cell antitumor function. Cancer Immunol Res. 2019;7(4):559–71. https://doi.org/10.1158/2326-6066.CIR-18-0637.CrossRefPubMedPubMedCentral

48.

Stanko K, Iwert C, Appelt C, Vogt K, Schumann J, Strunk FJ, et al. CD96 expression determines the inflammatory potential of IL-9-producing Th9 cells. Proc Natl Acad Sci U S A. 2018;115(13):E2940–e2949. https://doi.org/10.1073/pnas.1708329115.CrossRefPubMedPubMedCentral

49.

Xu F, Sunderland A, Zhou Y, Schulick RD, Edil BH, Zhu Y. Blockade of CD112R and TIGIT signaling sensitizes human natural killer cell functions. Cancer Immunol Immunother. 2017;66(10):1367–75. https://doi.org/10.1007/s00262-017-2031-x.CrossRefPubMedPubMedCentral

50.

Whelan S, Ophir E, Kotturi MF, Levy O, Ganguly S, Leung L, et al. PVRIG and PVRL2 are induced in Cancer and inhibit CD8(+) T-cell function. Cancer Immunol Res. 2019;7(2):257–68. https://doi.org/10.1158/2326-6066.CIR-18-0442.CrossRefPubMedPubMedCentral

51.

Tahara-Hanaoka S, Shibuya K, Kai H, Miyamoto A, Morikawa Y, Ohkochi N, et al. Tumor rejection by the poliovirus receptor family ligands of the DNAM-1 (CD226) receptor. Blood. 2006;107(4):1491–6. https://doi.org/10.1182/blood-2005-04-1684.CrossRefPubMed

52.

Chan CJ, Martinet L, Gilfillan S, Souza-Fonseca-Guimaraes F, Chow MT, Town L, et al. The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions. Nat Immunol. 2014;15(5):431–8. https://doi.org/10.1038/ni.2850.CrossRefPubMed

53.

Chan CJ, Andrews DM, McLaughlin NM, Yagita H, Gilfillan S, Colonna M, et al. DNAM-1/CD155 interactions promote cytokine and NK cell-mediated suppression of poorly immunogenic melanoma metastases. J Immunol. 2010;184(2):902–11. https://doi.org/10.4049/jimmunol.0903225.CrossRefPubMed

54.

Verhoeven DH, de Hooge AS, Mooiman EC, Santos SJ, ten Dam MM, Gelderblom H, et al. NK cells recognize and lyse Ewing sarcoma cells through NKG2D and DNAM-1 receptor dependent pathways. Mol Immunol. 2008;45(15):3917–25. https://doi.org/10.1016/j.molimm.2008.06.016.CrossRefPubMed

55.

Lakshmikanth T, Burke S, Ali TH, Kimpfler S, Ursini F, Ruggeri L, et al. NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo. J Clin Invest. 2009;119(5):1251–63. https://doi.org/10.1172/JCI36022.CrossRefPubMedPubMedCentral

56.

Pende D, Spaggiari GM, Marcenaro S, Martini S, Rivera P, Capobianco A, et al. Analysis of the receptor-ligand interactions in the natural killer-mediated lysis of freshly isolated myeloid or lymphoblastic leukemias: evidence for the involvement of the poliovirus receptor (CD155) and Nectin-2 (CD112). Blood. 2005;105(5):2066–73. https://doi.org/10.1182/blood-2004-09-3548.CrossRefPubMed

57.

Zhang Z, Su T, He L, Wang H, Ji G, Liu X, et al. Identification and functional analysis of ligands for natural killer cell activating receptors in colon carcinoma. Tohoku J Exp Med. 2012;226(1):59–68. https://doi.org/10.1620/tjem.226.59.CrossRefPubMed

58.

Carlsten M, Björkström NK, Norell H, Bryceson Y, van Hall T, Baumann BC, et al. DNAX accessory molecule-1 mediated recognition of freshly isolated ovarian carcinoma by resting natural killer cells. Cancer Res. 2007;67(3):1317–25. https://doi.org/10.1158/0008-5472.CAN-06-2264.CrossRefPubMed

59.

Platonova S, Cherfils-Vicini J, Damotte D, Crozet L, Vieillard V, Validire P, et al. Profound coordinated alterations of intratumoral NK cell phenotype and function in lung carcinoma. Cancer Res. 2011;71(16):5412–22. https://doi.org/10.1158/0008-5472.CAN-10-4179.CrossRefPubMed

60.

Iguchi-Manaka A, Okumura G, Ichioka E, Kiyomatsu H, Ikeda T, Bando H, et al. High expression of soluble CD155 in estrogen receptor-negative breast cancer. Breast Cancer. 2020;27(1):92–9. https://doi.org/10.1007/s12282-019-00999-8.CrossRefPubMed

61.

Morgado S, Sanchez-Correa B, Casado JG, Duran E, Gayoso I, Labella F, et al. NK cell recognition and killing of melanoma cells is controlled by multiple activating receptor-ligand interactions. J Innate Immun. 2011;3(4):365–73. https://doi.org/10.1159/000328505.CrossRefPubMed

62.

Hou S, Zheng X, Wei H, Tian Z, Sun R. Recombinant soluble CD226 protein directly inhibits cancer cell proliferation in vitro. Int Immunopharmacol. 2014;19(1):119–26. https://doi.org/10.1016/j.intimp.2014.01.012.CrossRefPubMed

63.

Yu X, Harden K, Gonzalez LC, Francesco M, Chiang E, Irving B, et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat Immunol. 2009;10(1):48–57. https://doi.org/10.1038/ni.1674.CrossRefPubMed

64.

Stanietsky N, Simic H, Arapovic J, Toporik A, Levy O, Novik A, et al. The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proc Natl Acad Sci U S A. 2009;106(42):17858–63. https://doi.org/10.1073/pnas.0903474106.CrossRefPubMedPubMedCentral

65.

Levin SD, Taft DW, Brandt CS, Bucher C, Howard ED, Chadwick EM, et al. Vstm3 is a member of the CD28 family and an important modulator of T-cell function. Eur J Immunol. 2011;41(4):902–15. https://doi.org/10.1002/eji.201041136.CrossRefPubMedPubMedCentral

66.

Wu H, Chen Y, Liu H, Xu LL, Teuscher P, Wang S, et al. Follicular regulatory T cells repress cytokine production by follicular helper T cells and optimize IgG responses in mice. Eur J Immunol. 2016;46(5):1152–61. https://doi.org/10.1002/eji.201546094.CrossRefPubMedPubMedCentral

67.

Boles KS, Vermi W, Facchetti F, Fuchs A, Wilson TJ, Diacovo TG, et al. A novel molecular interaction for the adhesion of follicular CD4 T cells to follicular DC. Eur J Immunol. 2009;39(3):695–703. https://doi.org/10.1002/eji.200839116.CrossRefPubMedPubMedCentral

68.

Takai Y, Irie K, Shimizu K, Sakisaka T, Ikeda W. Nectins and nectin-like molecules: roles in cell adhesion, migration, and polarization. Cancer Sci. 2003;94(8):655–67. https://doi.org/10.1111/j.1349-7006.2003.tb01499.x.CrossRefPubMed

69.

Nishiwada S, Sho M, Yasuda S, Shimada K, Yamato I, Akahori T, et al. Nectin-4 expression contributes to tumor proliferation, angiogenesis and patient prognosis in human pancreatic cancer. J Exp Clin Cancer Res. 2015;34(1):30. https://doi.org/10.1186/s13046-015-0144-7.CrossRefPubMedPubMedCentral

70.

Reches A, Ophir Y, Stein N, Kol I, Isaacson B, Charpak Amikam Y, et al. Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity. J Immunother Cancer. 2020;8(1):e000266. https://doi.org/10.1136/jitc-2019-000266.CrossRefPubMedPubMedCentral

71.

Liu S, Zhang H, Li M, Hu D, Li C, Ge B, et al. Recruitment of Grb2 and SHIP1 by the ITT-like motif of TIGIT suppresses granule polarization and cytotoxicity of NK cells. Cell Death Differ. 2013;20(3):456–64. https://doi.org/10.1038/cdd.2012.141.CrossRefPubMed

72.

Li M, Xia P, Du Y, Liu S, Huang G, Chen J, et al. T-cell immunoglobulin and ITIM domain (TIGIT) receptor/poliovirus receptor (PVR) ligand engagement suppresses interferon-γ production of natural killer cells via β-arrestin 2-mediated negative signaling. J Biol Chem. 2014;289(25):17647–57. https://doi.org/10.1074/jbc.M114.572420.CrossRefPubMedPubMedCentral

73.

Zhang C, Wang Y, Xun X, Wang S, Xiang X, Hu S, et al. TIGIT can exert immunosuppressive effects on CD8+ T cells by the CD155/TIGIT signaling pathway for hepatocellular carcinoma in vitro. J Immunother. 2020;43(8):236–43. https://doi.org/10.1097/CJI.0000000000000330.CrossRefPubMedPubMedCentral

74.

Kurtulus S, Sakuishi K, Ngiow SF, Joller N, Tan DJ, Teng MW, et al. TIGIT predominantly regulates the immune response via regulatory T cells. J Clin Invest. 2015;125(11):4053–62. https://doi.org/10.1172/JCI81187.CrossRefPubMedPubMedCentral

75.

Joller N, Lozano E, Burkett PR, Patel B, Xiao S, Zhu C, et al. Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses. Immunity. 2014;40(4):569–81. https://doi.org/10.1016/j.immuni.2014.02.012.CrossRefPubMedPubMedCentral

76.

De Vlaeminck Y, González-Rascón A, Goyvaerts C, Breckpot K. Cancer-associated myeloid regulatory cells. Front Immunol. 2016;7:113.CrossRef

77.

Deuss FA, Watson GM, Fu Z, Rossjohn J, Berry R. Structural Basis for CD96 Immune Receptor Recognition of Nectin-like Protein-5, CD155. Structure. 2019;27:219–28 e213.CrossRef

78.

Lozano E, Dominguez-Villar M, Kuchroo V, Hafler DA. The TIGIT/CD226 axis regulates human T cell function. J Immunol. 2012;188(8):3869–75. https://doi.org/10.4049/jimmunol.1103627.CrossRefPubMed

79.

Johnston RJ, Comps-Agrar L, Hackney J, Yu X, Huseni M, Yang Y, et al. The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function. Cancer Cell. 2014;26(6):923–37. https://doi.org/10.1016/j.ccell.2014.10.018.CrossRefPubMed

80.

Stanietsky N, Rovis TL, Glasner A, Seidel E, Tsukerman P, Yamin R, et al. Mouse TIGIT inhibits NK-cell cytotoxicity upon interaction with PVR. Eur J Immunol. 2013;43(8):2138–50. https://doi.org/10.1002/eji.201243072.CrossRefPubMedPubMedCentral

81.

Wang F, Hou H, Wu S, Tang Q, Liu W, Huang M, et al. TIGIT expression levels on human NK cells correlate with functional heterogeneity among healthy individuals. Eur J Immunol. 2015;45(10):2886–97. https://doi.org/10.1002/eji.201545480.CrossRefPubMed

82.

Sarhan D, Cichocki F, Zhang B, Yingst A, Spellman SR, Cooley S, et al. Adaptive NK cells with low TIGIT expression are inherently resistant to myeloid-derived suppressor cells. Cancer Res. 2016;76(19):5696–706. https://doi.org/10.1158/0008-5472.CAN-16-0839.CrossRefPubMedPubMedCentral

83.

Kong Y, Zhu L, Schell TD, Zhang J, Claxton DF, Ehmann WC, et al. T-cell immunoglobulin and ITIM domain (TIGIT) associates with CD8+ T-cell exhaustion and poor clinical outcome in AML patients. Clin Cancer Res. 2016;22(12):3057–66. https://doi.org/10.1158/1078-0432.CCR-15-2626.CrossRefPubMed

84.

Wang PL, O'Farrell S, Clayberger C, Krensky AM. Identification and molecular cloning of tactile. A novel human T cell activation antigen that is a member of the Ig gene superfamily. J Immunol. 1992;148:2600–8.PubMed

85.

McVicar DW, Burshtyn DN. Intracellular signaling by the killer immunoglobulin-like receptors and Ly49. Sci STKE. 2001;2001:re1.PubMed

86.

Meyer D, Seth S, Albrecht J, Maier MK, du Pasquier L, Ravens I, et al. CD96 interaction with CD155 via its first Ig-like domain is modulated by alternative splicing or mutations in distal Ig-like domains. J Biol Chem. 2009;284(4):2235–44. https://doi.org/10.1074/jbc.M807698200.CrossRefPubMed

87.

Garg S, Madkaikar M, Ghosh K. Investigating cell surface markers on normal hematopoietic stem cells in three different niche conditions. Int J Stem Cells. 2013;6(2):129–33. https://doi.org/10.15283/ijsc.2013.6.2.129.CrossRefPubMedPubMedCentral

88.

Seth S, Maier MK, Qiu Q, Ravens I, Kremmer E, Förster R, et al. The murine pan T cell marker CD96 is an adhesion receptor for CD155 and nectin-1. Biochem Biophys Res Commun. 2007;364(4):959–65. https://doi.org/10.1016/j.bbrc.2007.10.102.CrossRefPubMed

89.

Fuchs A, Cella M, Giurisato E, Shaw AS, Colonna M. Cutting edge: CD96 (tactile) promotes NK cell-target cell adhesion by interacting with the poliovirus receptor (CD155). J Immunol. 2004;172(7):3994–8. https://doi.org/10.4049/jimmunol.172.7.3994.CrossRefPubMed

90.

Lenac Rovis T, Kucan Brlic P, Kaynan N, Juranic Lisnic V, Brizic I, Jordan S, et al. Inflammatory monocytes and NK cells play a crucial role in DNAM-1-dependent control of cytomegalovirus infection. J Exp Med. 2016;213(9):1835–50. https://doi.org/10.1084/jem.20151899.CrossRefPubMedPubMedCentral

91.

Fuchs A, Cella M, Kondo T, Colonna M. Paradoxic inhibition of human natural interferon-producing cells by the activating receptor NKp44. Blood. 2005;106(6):2076–82. https://doi.org/10.1182/blood-2004-12-4802.CrossRefPubMed

92.

Jang IK, Zhang J, Chiang YJ, Kole HK, Cronshaw DG, Zou Y, et al. Grb2 functions at the top of the T-cell antigen receptor-induced tyrosine kinase cascade to control thymic selection. Proc Natl Acad Sci U S A. 2010;107(23):10620–5. https://doi.org/10.1073/pnas.0905039107.CrossRefPubMedPubMedCentral

93.

Wange RL, Samelson LE. Complex complexes: signaling at the TCR. Immunity. 1996;5(3):197–205. https://doi.org/10.1016/S1074-7613(00)80315-5.CrossRefPubMed

94.

Adachi K, Davis MM. T-cell receptor ligation induces distinct signaling pathways in naive vs. antigen-experienced T cells. Proc Natl Acad Sci U S A. 2011;108(4):1549–54. https://doi.org/10.1073/pnas.1017340108.CrossRefPubMedPubMedCentral

95.

Boomer JS, Green JM. An enigmatic tail of CD28 signaling. Cold Spring Harb Perspect Biol. 2010;2:a002436.CrossRef

96.

Peng YP, Xi CH, Zhu Y, Yin LD, Wei JS, Zhang JJ, et al. Altered expression of CD226 and CD96 on natural killer cells in patients with pancreatic cancer. Oncotarget. 2016;7(41):66586–94. https://doi.org/10.18632/oncotarget.11953.CrossRefPubMedPubMedCentral

97.

Zhu Y, Paniccia A, Schulick AC, Chen W, Koenig MR, Byers JT, et al. Identification of CD112R as a novel checkpoint for human T cells. J Exp Med. 2016;213(2):167–76. https://doi.org/10.1084/jem.20150785.CrossRefPubMedPubMedCentral

98.

Billadeau DD, Leibson PJ. ITAMs versus ITIMs: striking a balance during cell regulation. J Clin Invest. 2002;109(2):161–8. https://doi.org/10.1172/JCI0214843.CrossRefPubMedPubMedCentral

Title: Poliovirus receptor (PVR)-like protein cosignaling network: new opportunities for cancer immunotherapy
Authors: Baokang Wu
Chongli Zhong
Qi Lang
Zhiyun Liang
Yizhou Zhang
Xin Zhao
Yang Yu
Heming Zhang
Feng Xu
Yu Tian
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Polio Virus
Cancer Immunotherapy
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2021
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-021-02068-5

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