Abstract
Poliovirus receptor (PVR, CD155) has recently been gaining scientific interest as a therapeutic target in the field of tumor immunology due to its prominent endogenous and immune functions. In contrast to healthy tissues, PVR is expressed at high levels in several human malignancies and seems to have protumorigenic and therapeutically attractive properties that are currently being investigated in the field of recombinant oncolytic virotherapy. More intriguingly, PVR participates in a considerable number of immunoregulatory functions through its interactions with activating and inhibitory immune cell receptors. These functions are often modified in the tumor microenvironment, contributing to tumor immunosuppression. Indeed, increasing evidence supports the rationale for developing strategies targeting these interactions, either in terms of checkpoint therapy (i.e., targeting inhibitory receptors) or in adoptive cell therapy, which targets PVR as a tumor marker.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Takai, Y., Miyoshi, J., Ikeda, W. & Ogita, H. Nectins and nectin-like molecules: roles in contact inhibition of cell movement and proliferation. Nat. Rev. Mol. Cell Biol. 9, 603–615 (2008).
Gromeier, M., Lachmann, S., Rosenfeld, M. R., Gutin, P. H. & Wimmer, E. Intergeneric poliovirus recombinants for the treatment of malignant glioma. Proc. Natl Acad. Sci. USA 97, 6803–6808 (2000).
Masson, D. et al. Overexpression of the CD155 gene in human colorectal carcinoma. Gut 49, 236–240 (2001).
Castriconi, R. et al. Natural killer cell-mediated killing of freshly isolated neuroblastoma cells: critical role of DNAX accessory molecule-1-poliovirus receptor interaction. Cancer Res. 64, 9180–9184 (2004).
Pende, D. 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 105, 2066–2073 (2005).
Carlsten, M. et al. Primary human tumor cells expressing CD155 impair tumor targeting by down-regulating DNAM-1 on NK cells. J. Immunol. 183, 4921–4930 (2009).
Sloan, K. E., Stewart, J. K., Treloar, A. F., Matthews, R. T. & Jay, D. G. CD155/PVR enhances glioma cell dispersal by regulating adhesion signaling and focal adhesion dynamics. Cancer Res. 65, 10930–10937 (2005).
Kono, T. et al. The CD155/poliovirus receptor enhances the proliferation of ras-mutated cells. Int. J. Cancer 122, 317–324 (2008).
Martinet, L. & Smyth, M. J. Balancing natural killer cell activation through paired receptors. Nat. Rev. Immunol. 15, 243–254 (2015).
Nishiwada, S. et al. Clinical significance of CD155 expression in human pancreatic cancer. Anticancer Res. 35, 2287–2297 (2015).
Bowers, J. R., Readler, J. M., Sharma, P. & Excoffon, K. Poliovirus receptor: more than a simple viral receptor. Virus Res. 242, 1–6 (2017).
Carlsten, M. et al. Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34+ blasts in myelodysplastic syndrome. Leukemia 24, 1607–1616 (2010).
Li, X. Y. et al. CD155 loss enhances tumor suppression via combined host and tumor-intrinsic mechanisms. J. Clin. Invest. 128, 2613–2625 (2018).
Bronte, V. The expanding constellation of immune checkpoints: a DNAMic control by CD155. J. Clin. Invest. 128, 2199–2201 (2018).
Gao, J., Zheng, Q., Xin, N., Wang, W. & Zhao, C. CD155, an onco-immunologic molecule in human tumors. Cancer Sci. 108, 1934–1938 (2017).
Mendelsohn, C. L., Wimmer, E. & Racaniello, V. R. Cellular receptor for poliovirus: molecular cloning, nucleotide sequence, and expression of a new member of the immunoglobulin superfamily. Cell 56, 855–865 (1989).
Stengel, K. F. et al. Structure of TIGIT immunoreceptor bound to poliovirus receptor reveals a cell-cell adhesion and signaling mechanism that requires cis-trans receptor clustering. Proc. Natl Acad. Sci. USA 109, 5399–5404 (2012).
Koike, S. et al. The poliovirus receptor protein is produced both as membrane-bound and secreted forms. EMBO J. 9, 3217–3224 (1990).
Baury, B. et al. Identification of secreted CD155 isoforms. Biochem. Biophys. Res. Commun. 309, 175–182 (2003).
Iguchi-Manaka, A. et al. Increased soluble CD155 in the serum of cancer patients. PLoS ONE 11, e0152982 (2016).
Deng, W. et al. Antitumor immunity. A shed NKG2D ligand that promotes natural killer cell activation and tumor rejection. Science 348, 136–139 (2015).
Groh, V., Wu, J., Yee, C. & Spies, T. Tumour-derived soluble MIC ligands impair expression of NKG2D and T cell activation. Nature 419, 734–738 (2002).
Zhu, X. & Lang, J. Soluble PD-1 and PD-L1: predictive and prognostic significance in cancer. Oncotarget 8, 97671–97682 (2017).
Oda, T., Ohka, S. & Nomoto, A. Ligand stimulation of CD155alpha inhibits cell adhesion and enhances cell migration in fibroblasts. Biochem. Biophys. Res. Commun. 319, 1253–1264 (2004).
Ohka, S., Ohno, H., Tohyama, K. & Nomoto, A. Basolateral sorting of human poliovirus receptor alpha involves an interaction with the mu1B subunit of the clathrin adaptor complex in polarized epithelial cells. Biochem. Biophys. Res. Commun. 287, 941–948 (2001).
Yusa, S., Catina, T. L. & Campbell, K. S. SHP-1- and phosphotyrosine-independent inhibitory signaling by a killer cell Ig-like receptor cytoplasmic domain in human NK cells. J. Immunol. 168, 5047–5057 (2002).
Lange, R., Peng, X., Wimmer, E., Lipp, M. & Bernhardt, G. The poliovirus receptor CD155 mediates cell-to-matrix contacts by specifically binding to vitronectin. Virology 285, 218–227 (2001).
Reymond, N. et al. DNAM-1 and PVR regulate monocyte migration through endothelial junctions. J. Exp. Med. 199, 1331–1341 (2004).
Sullivan, D. P., Seidman, M. A. & Muller, W. A. Poliovirus receptor (CD155) regulates a step in transendothelial migration between PECAM and CD99. Am. J. Pathol. 182, 1031–1042 (2013).
Kakunaga, S. et al. Enhancement of serum- and platelet-derived growth factor-induced cell proliferation by Necl-5/Tage4/poliovirus receptor/CD155 through the Ras-Raf-MEK-ERK signaling. J. Biol. Chem. 279, 36419–36425 (2004).
Ikeda, W. et al. Nectin-like molecule-5/Tage4 enhances cell migration in an integrin-dependent, Nectin-3-independent manner. J. Biol. Chem. 279, 18015–18025 (2004).
Minami, Y. et al. Necl-5/poliovirus receptor interacts in cis with integrin alphaVbeta3 and regulates its clustering and focal complex formation. J. Biol. Chem. 282, 18481–18496 (2007).
Kajita, M., Ikeda, W., Tamaru, Y. & Takai, Y. Regulation of platelet-derived growth factor-induced Ras signaling by poliovirus receptor Necl-5 and negative growth regulator Sprouty2. Genes Cells 12, 345–357 (2007).
Lee, E. et al. Inhibition of breast cancer growth and metastasis by a biomimetic peptide. Sci. Rep. 4, 7139 (2014).
Kinugasa, M. et al. Necl-5/poliovirus receptor interacts with VEGFR2 and regulates VEGF-induced angiogenesis. Circ. Res. 110, 716–726 (2012).
Campbell, H. K., Maiers, J. L. & DeMali, K. A. Interplay between tight junctions & adherens junctions. Exp. Cell Res. 358, 39–44 (2017).
Fujito, T. et al. Inhibition of cell movement and proliferation by cell-cell contact-induced interaction of Necl-5 with nectin-3. J. Cell Biol. 171, 165–173 (2005).
Stanietsky, N. & Mandelboim, O. Paired NK cell receptors controlling NK cytotoxicity. FEBS Lett. 584, 4895–4900 (2010).
Bottino, C. 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. 198, 557–567 (2003).
Chan, C. J. et al. The receptors CD96 and CD226 oppose each other in the regulation of natural killer cell functions. Nat. Immunol. 15, 431–438 (2014).
de Andrade, L. F., Smyth, M. J. & Martinet, L. DNAM-1 control of natural killer cells functions through nectin and nectin-like proteins. Immunol. Cell Biol. 92, 237–244 (2014).
Shibuya, A. et al. DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes. Immunity 4, 573–581 (1996).
Anderson, A. C., Joller, N. & Kuchroo, V. K. Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. Immunity 44, 989–1004 (2016).
Joller, N. et al. Cutting edge: TIGIT has T cell-intrinsic inhibitory functions. J. Immunol. 186, 1338–1342 (2011).
Stanietsky, N. et al. The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proc. Natl Acad. Sci. USA 106, 17858–17863 (2009).
Yu, X. et al. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. Nat. Immunol. 10, 48–57 (2009).
Dougall, W. C., Kurtulus, S., Smyth, M. J. & Anderson, A. C. TIGIT and CD96: new checkpoint receptor targets for cancer immunotherapy. Immunol. Rev. 276, 112–120 (2017).
Blake, S. J. et al. Suppression of metastases using a new lymphocyte checkpoint target for cancer immunotherapy. Cancer Discov. 6, 446–459 (2016).
Fuchs, A., Cella, M., Giurisato, E., Shaw, A. S. & Colonna, M. Cutting edge: CD96 (tactile) promotes NK cell-target cell adhesion by interacting with the poliovirus receptor (CD155). J. Immunol. 172, 3994–3998 (2004).
Stanko, K. et al. CD96 expression determines the inflammatory potential of IL-9-producing Th9 cells. Proc. Natl Acad. Sci. USA 115, E2940–E2949 (2018).
Denis, M. G. Characterization, cloning and expression of the Tage4 gene, a member of the immunoglobulin superfamily. Int. J. Oncol. 12, 997–1005 (1998).
Lim, Y. P., Fowler, L. C., Hixson, D. C., Wehbe, T. & Thompson, N. L. TuAg.1 is the liver isoform of the rat colon tumor-associated antigen pE4 and a member of the immunoglobulin-like supergene family. Cancer Res. 56, 3934–3940 (1996).
Nakai, R. et al. Overexpression of Necl-5 correlates with unfavorable prognosis in patients with lung adenocarcinoma. Cancer Sci. 101, 1326–1330 (2010).
Bevelacqua, V. et al. Nectin like-5 overexpression correlates with the malignant phenotype in cutaneous melanoma. Oncotarget 3, 882–892 (2012).
Inozume, T. et al. Melanoma cells control antimelanoma CTL responses via interaction between TIGIT and CD155 in the effector phase. J. Invest. Dermatol. 136, 255–263 (2016).
Huang, D. W., Huang, M., Lin, X. S. & Huang, Q. CD155 expression and its correlation with clinicopathologic characteristics, angiogenesis, and prognosis in human cholangiocarcinoma. Onco. Targets Ther. 10, 3817–3825 (2017).
Hirota, T., Irie, K., Okamoto, R., Ikeda, W. & Takai, Y. Transcriptional activation of the mouse Necl-5/Tage4/PVR/CD155 gene by fibroblast growth factor or oncogenic Ras through the Raf-MEK-ERK-AP-1 pathway. Oncogene 24, 2229–2235 (2005).
Solecki, D. J., Gromeier, M., Mueller, S., Bernhardt, G. & Wimmer, E. Expression of the human poliovirus receptor/CD155 gene is activated by sonic hedgehog. J. Biol. Chem. 277, 25697–25702 (2002).
Gorgoulis, V. G. et al. Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 434, 907–913 (2005).
Soriani, A. et al. ATM-ATR-dependent up-regulation of DNAM-1 and NKG2D ligands on multiple myeloma cells by therapeutic agents results in enhanced NK-cell susceptibility and is associated with a senescent phenotype. Blood 113, 3503–3511 (2009).
Soriani, A. et al. Chemotherapy-elicited upregulation of NKG2D and DNAM-1 ligands as a therapeutic target in multiple myeloma. Oncoimmunology 2, e26663 (2013).
Atsumi, S. et al. Prognostic significance of CD155 mRNA expression in soft tissue sarcomas. Oncol. Lett. 5, 1771–1776 (2013).
Tane, S. et al. The role of Necl-5 in the invasive activity of lung adenocarcinoma. Exp. Mol. Pathol. 94, 330–335 (2013).
Sloan, K. E. et al. CD155/PVR plays a key role in cell motility during tumor cell invasion and migration. BMC Cancer 4, 73 (2004).
Zheng, Q. et al. CD155 knockdown promotes apoptosis via AKT/Bcl-2/Bax in colon cancer cells. J. Cell. Mol. Med. 22, 131–140 (2018).
Escalante, N. K., von Rossum, A., Lee, M. & Choy, J. C. CD155 on human vascular endothelial cells attenuates the acquisition of effector functions in CD8 T cells. Arterioscler. Thromb. Vasc. Biol. 31, 1177–1184 (2011).
Merrill, M. K. et al. Poliovirus receptor CD155-targeted oncolysis of glioma. Neuro. Oncol. 6, 208–217 (2004).
Iwasaki, A. et al. Immunofluorescence analysis of poliovirus receptor expression in Peyer’s patches of humans, primates, and CD155 transgenic mice: implications for poliovirus infection. J. Infect. Dis. 186, 585–592 (2002).
Iguchi-Manaka, A. et al. Accelerated tumor growth in mice deficient in DNAM-1 receptor. J. Exp. Med. 205, 2959–2964 (2008).
Gilfillan, S. et al. DNAM-1 promotes activation of cytotoxic lymphocytes by nonprofessional antigen-presenting cells and tumors. J. Exp. Med. 205, 2965–2973 (2008).
Shibuya, K. 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. 198, 1829–1839 (2003).
Tahara-Hanaoka, S. et al. Tumor rejection by the poliovirus receptor family ligands of the DNAM-1 (CD226) receptor. Blood 107, 1491–1496 (2006).
Seth, S. et al. Heterogeneous expression of the adhesion receptor CD226 on murine NK and T cells and its function in NK-mediated killing of immature dendritic cells. J. Leukoc. Biol. 86, 91–101 (2009).
Smith, L. E. et al. Sensitivity of dendritic cells to NK-mediated lysis depends on the inflammatory environment and is modulated by CD54/CD226-driven interactions. J. Leukoc. Biol. 100, 781–789 (2016).
Bachelet, I., Munitz, A., Mankutad, D. & Levi-Schaffer, F. Mast cell costimulation by CD226/CD112 (DNAM-1/Nectin-2): a novel interface in the allergic process. J. Biol. Chem. 281, 27190–27196 (2006).
Pende, D. et al. Expression of the DNAM-1 ligands, Nectin-2 (CD112) and poliovirus receptor (CD155), on dendritic cells: relevance for natural killer-dendritic cell interaction. Blood 107, 2030–2036 (2006).
Kojima, H. et al. CD226 mediates platelet and megakaryocytic cell adhesion to vascular endothelial cells. J. Biol. Chem. 278, 36748–36753 (2003).
Mamessier, E. et al. Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity. J. Clin. Invest. 121, 3609–3622 (2011).
Pievani, A. et al. Dual-functional capability of CD3+ CD56 + CIK cells, a T-cell subset that acquires NK function and retains TCR-mediated specific cytotoxicity. Blood 118, 3301–3310 (2011).
Wu, M. R., Zhang, T., Alcon, A. & Sentman, C. L. DNAM-1-based chimeric antigen receptors enhance T cell effector function and exhibit in vivo efficacy against melanoma. Cancer Immunol. Immunother. 64, 409–418 (2015).
Lenac Rovis, T. et al. Inflammatory monocytes and NK cells play a crucial role in DNAM-1-dependent control of cytomegalovirus infection. J. Exp. Med. 213, 1835–1850 (2016).
Joller, N. et al. Treg cells expressing the coinhibitory molecule TIGIT selectively inhibit proinflammatory Th1 and Th17 cell responses. Immunity 40, 569–581 (2014).
Johnston, R. J. et al. The immunoreceptor TIGIT regulates antitumor and antiviral CD8(+) T cell effector function. Cancer Cell 26, 923–937 (2014).
Pauken, K. E. & Wherry, E. J. TIGIT and CD226: tipping the balance between costimulatory and coinhibitory molecules to augment the cancer immunotherapy toolkit. Cancer Cell 26, 785–787 (2014).
Blake, S. J., Dougall, W. C., Miles, J. J., Teng, M. W. & Smyth, M. J. Molecular pathways: targeting CD96 and TIGIT for cancer immunotherapy. Clin. Cancer Res. 22, 5183–5188 (2016).
Wang, P. L., O’Farrell, S., Clayberger, C. & Krensky, A. M. Identification and molecular cloning of tactile. A novel human T cell activation antigen that is a member of the Ig gene superfamily. J. Immunol. 148, 2600–2608 (1992).
Zhang, W. et al. Expressions of CD96 and CD123 in bone marrow cells of patients with myelodysplastic syndromes. Clin. Lab. 61, 1429–1434 (2015).
Hosen, N. et al. CD96 is a leukemic stem cell-specific marker in human acute myeloid leukemia. Proc. Natl Acad. Sci. USA 104, 11008–11013 (2007).
Gramatzki, M. et al. Antibodies TC-12 (“unique”) and TH-111 (CD96) characterize T-cell acute lymphoblastic leukemia and a subgroup of acute myeloid leukemia. Exp. Hematol. 26, 1209–1214 (1998).
Stanietsky, N. et al. Mouse TIGIT inhibits NK-cell cytotoxicity upon interaction with PVR. Eur. J. Immunol. 43, 2138–2150 (2013).
McVicar, D. W. & Burshtyn, D. N. Intracellular signaling by the killer immunoglobulin-like receptors and Ly49. Sci. STKE 2001, re1 (2001).
Roman Aguilera, A. et al. CD96 targeted antibodies need not block CD96-CD155 interactions to promote NK cell anti-metastatic activity. Oncoimmunology 7, e1424677 (2018).
Fukuhara, H., Ino, Y. & Todo, T. Oncolytic virus therapy: a new era of cancer treatment at dawn. Cancer Sci. 107, 1373–1379 (2016).
Kaufman, H. L., Kohlhapp, F. J. & Zloza, A. Oncolytic viruses: a new class of immunotherapy drugs. Nat. Rev. Drug Discov. 14, 642–662 (2015).
Desjardins, A. et al. Recurrent glioblastoma treated with recombinant poliovirus. N. Engl. J. Med. 379, 150–161 (2018).
Hogle, J. M. Poliovirus cell entry: common structural themes in viral cell entry pathways. Annu. Rev. Microbiol. 56, 677–702 (2002).
Lwoff, A., Dulbecco, R., Vogt, M. & Lwoff, M. Kinetics of the release of poliomyelitis virus from single cells. Ann. N. Y. Acad. Sci. 61, 801–805 (1955).
Daley, J. K., Gechman, L. A., Skipworth, J. & Rall, G. F. Poliovirus replication and spread in primary neuron cultures. Virology 340, 10–20 (2005).
Chandramohan, V. et al. Validation of an immunohistochemistry assay for detection of CD155, the poliovirus receptor, in malignant gliomas. Arch. Pathol. Lab. Med. 141, 1697–1704 (2017).
Bodian, D. Emerging concept of poliomyelitis infection. Science 122, 105–108 (1955).
Sabin, A. B. Pathogenesis of poliomyelitis; reappraisal in the light of new data. Science 123, 1151–1157 (1956).
Kauder, S. E. & Racaniello, V. R. Poliovirus tropism and attenuation are determined after internal ribosome entry. J. Clin. Invest. 113, 1743–1753 (2004).
Ida-Hosonuma, M. et al. The alpha/beta interferon response controls tissue tropism and pathogenicity of poliovirus. J. Virol. 79, 4460–4469 (2005).
Georgescu, M. M. et al. Evolution of the Sabin type 1 poliovirus in humans: characterization of strains isolated from patients with vaccine-associated paralytic poliomyelitis. J. Virol. 71, 7758–7768 (1997).
Wimmer, E., Hellen, C. U. & Cao, X. Genetics of poliovirus. Annu. Rev. Genet. 27, 353–436 (1993).
Gromeier, M., Alexander, L. & Wimmer, E. Internal ribosomal entry site substitution eliminates neurovirulence in intergeneric poliovirus recombinants. Proc. Natl Acad. Sci. USA 93, 2370–2375 (1996).
Merrill, M. K., Dobrikova, E. Y. & Gromeier, M. Cell-type-specific repression of internal ribosome entry site activity by double-stranded RNA-binding protein 76. J. Virol. 80, 3147–3156 (2006).
Merrill, M. K. & Gromeier, M. The double-stranded RNA binding protein 76:NF45 heterodimer inhibits translation initiation at the rhinovirus type 2 internal ribosome entry site. J. Virol. 80, 6936–6942 (2006).
Neplioueva, V., Dobrikova, E. Y., Mukherjee, N., Keene, J. D. & Gromeier, M. Tissue type-specific expression of the dsRNA-binding protein 76 and genome-wide elucidation of its target mRNAs. PLoS ONE 5, e11710 (2010).
Brown, M. C. & Gromeier, M. Cytotoxic and immunogenic mechanisms of recombinant oncolytic poliovirus. Curr. Opin. Virol. 13, 81–85 (2015).
Gromeier, M., Bossert, B., Arita, M., Nomoto, A. & Wimmer, E. Dual stem loops within the poliovirus internal ribosomal entry site control neurovirulence. J. Virol. 73, 958–964 (1999).
Campbell, S. A., Lin, J., Dobrikova, E. Y. & Gromeier, M. Genetic determinants of cell type-specific poliovirus propagation in HEK 293 cells. J. Virol. 79, 6281–6290 (2005).
Goetz, C., Dobrikova, E., Shveygert, M., Dobrikov, M. & Gromeier, M. Oncolytic poliovirus against malignant glioma. Future Virol. 6, 1045–1058 (2011).
Thompson, E. M. et al. Poliovirus receptor (CD155) expression in pediatric brain tumors mediates oncolysis of medulloblastoma and pleomorphic xanthoastrocytoma. J. Neuropathol. Exp. Neurol. 77, 696–702 (2018).
Cello, J. et al. Growth phenotypes and biosafety profiles in poliovirus-receptor transgenic mice of recombinant oncolytic polio/human rhinoviruses. J. Med. Virol. 80, 352–359 (2008).
Abe, Y. et al. The toll-like receptor 3-mediated antiviral response is important for protection against poliovirus infection in poliovirus receptor transgenic mice. J. Virol. 86, 185–194 (2012).
Kotla, S. & Gustin, K. E. Proteolysis of MDA5 and IPS-1 is not required for inhibition of the type I IFN response by poliovirus. Virol. J. 12, 158 (2015).
Dodd, D. A., Giddings, T. H. Jr & Kirkegaard, K. Poliovirus 3A protein limits interleukin-6 (IL-6), IL-8, and beta interferon secretion during viral infection. J. Virol. 75, 8158–8165 (2001).
Morrison, J. M. & Racaniello, V. R. Proteinase 2Apro is essential for enterovirus replication in type I interferon-treated cells. J. Virol. 83, 4412–4422 (2009).
Brown, M. C. et al. Oncolytic polio virotherapy of cancer. Cancer 120, 3277–3286 (2014).
Brown, M. C. et al. Cancer immunotherapy with recombinant poliovirus induces IFN-dominant activation of dendritic cells and tumor antigen-specific CTLs. Sci. Transl. Med. 9, eaan4220 (2017).
Holl, E. K. et al. Recombinant oncolytic poliovirus, PVSRIPO, has potent cytotoxic and innate inflammatory effects, mediating therapy in human breast and prostate cancer xenograft models. Oncotarget 7, 79828–79841 (2016).
Toyoda, H., Wimmer, E. & Cello, J. Oncolytic poliovirus therapy and immunization with poliovirus-infected cell lysate induces potent antitumor immunity against neuroblastoma in vivo. Int. J. Oncol. 38, 81–87 (2011).
Castriconi, R. et al. NK cells recognize and kill human glioblastoma cells with stem cell-like properties. J. Immunol. 182, 3530–3539 (2009).
Maherally, Z., Smith, J. R., An, Q. & Pilkington, G. J. Receptors for hyaluronic acid and poliovirus: a combinatorial role in glioma invasion? PLoS ONE 7, e30691 (2012).
Enloe, B. M. & Jay, D. G. Inhibition of Necl-5 (CD155/PVR) reduces glioblastoma dispersal and decreases MMP-2 expression and activity. J. Neurooncol. 102, 225–235 (2011).
Gromeier, M., Solecki, D., Patel, D. D. & Wimmer, E. Expression of the human poliovirus receptor/CD155 gene during development of the central nervous system: implications for the pathogenesis of poliomyelitis. Virology 273, 248–257 (2000).
Toyoda, H., Yin, J., Mueller, S., Wimmer, E. & Cello, J. Oncolytic treatment and cure of neuroblastoma by a novel attenuated poliovirus in a novel poliovirus-susceptible animal model. Cancer Res. 67, 2857–2864 (2007).
Dobrikova, E. Y. et al. Recombinant oncolytic poliovirus eliminates glioma in vivo without genetic adaptation to a pathogenic phenotype. Mol. Ther. 16, 1865–1872 (2008).
Denniston, E. et al. The practical consideration of poliovirus as an oncolytic virotherapy. Am. J. Virol. 5, 1–7 (2016).
Drake, C. G., Jaffee, E. & Pardoll, D. M. Mechanisms of immune evasion by tumors. Adv. Immunol. 90, 51–81 (2006).
Strohl, W. R. Current progress in innovative engineered antibodies. Protein Cell 9, 86–120 (2018).
Mahmoudi, M. & Farokhzad, O. C. Cancer immunotherapy: wound-bound checkpoint blockade. Nat. Biomed. Eng. 1, 0031 (2017).
Leach, D. R., Krummel, M. F. & Allison, J. P. Enhancement of antitumor immunity by CTLA-4 blockade. Science 271, 1734–1736 (1996).
Freeman, G. J. 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. 192, 1027–1034 (2000).
Chen, L. & Han, X. Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. J. Clin. Invest. 125, 3384–3391 (2015).
Callahan, M. K. & Wolchok, J. D. At the bedside: CTLA-4- and PD-1-blocking antibodies in cancer immunotherapy. J. Leukoc. Biol. 94, 41–53 (2013).
Burugu, S., Dancsok, A. R. & Nielsen, T. O. Emerging targets in cancer immunotherapy. Semin Cancer Biol. (2017). https://doi.org/10.1016/j.semcancer.2017.10.001.
Chauvin, J. M. et al. TIGIT and PD-1 impair tumor antigen-specific CD8(+) T cells in melanoma patients. J. Clin. Invest. 125, 2046–2058 (2015).
Dixon, K. O. et al. Functional anti-TIGIT antibodies regulate development of autoimmunity and antitumor immunity. J. Immunol. 200, 3000–3007 (2018).
Kurtulus, S. et al. TIGIT predominantly regulates the immune response via regulatory T cells. J. Clin. Invest. 125, 4053–4062 (2015).
Zhang, Q. et al. Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity. Nat. Immunol. (2018).
Georgiev, H., Ravens, I., Papadogianni, G. & Bernhardt, G. Coming of age: CD96 emerges as modulator of immune responses. Front. Immunol. 9, 1072 (2018).
Barrow, A. D. et al. Natural killer cells control tumor growth by sensing a growth factor. Cell 172, 534–48 e19 (2018).
Harjunpaa, H. et al. Deficiency of host CD96 and PD-1 or TIGIT enhances tumor immunity without significantly compromising immune homeostasis. Oncoimmunology 7, e1445949 (2018).
Meyer, D. 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. 284, 2235–2244 (2009).
Seth, S. et al. The murine pan T cell marker CD96 is an adhesion receptor for CD155 and nectin-1. Biochem. Biophys. Res. Commun. 364, 959–965 (2007).
Carlsten, M. et al. DNAX accessory molecule-1 mediated recognition of freshly isolated ovarian carcinoma by resting natural killer cells. Cancer Res. 67, 1317–1325 (2007).
El-Sherbiny, Y. M. et al. The requirement for DNAM-1, NKG2D, and NKp46 in the natural killer cell-mediated killing of myeloma cells. Cancer Res. 67, 8444–8449 (2007).
Peng, Y. P. et al. Altered expression of CD226 and CD96 on natural killer cells in patients with pancreatic cancer. Oncotarget 7, 66586–66594 (2016).
Coustan-Smith, E. et al. Universal monitoring of minimal residual disease in acute myeloid leukemia. JCI Insight 3, 98561 (2018).
Michot, J. M. et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur. J. Cancer 54, 139–148 (2016).
Kourie, H. R. & Klastersky, J. Immune checkpoint inhibitors side effects and management. Immunotherapy 8, 799–807 (2016).
Zang, Y. W., Gu, X. D., Xiang, J. B. & Chen, Z. Y. Clinical application of adoptive T cell therapy in solid tumors. Med. Sci. Monit. 20, 953–959 (2014).
Kunert, A. & Debets, R. Engineering T cells for adoptive therapy: outsmarting the tumor. Curr. Opin. Immunol. 51, 133–139 (2018).
Dai, H., Wang, Y., Lu, X. & Han, W. Chimeric antigen receptors modified T-cells for cancer therapy. J. Natl Cancer Inst. 108, djv439 (2016).
Iyer, R. K., Bowles, P. A., Kim, H. & Dulgar-Tulloch, A. Industrializing autologous adoptive immunotherapies: manufacturing advances and challenges. Front. Med. 5, 150 (2018).
Kosti, P., Maher, J. & Arnold, J. N. Perspectives on chimeric antigen receptor T-cell immunotherapy for solid tumors. Front. Immunol. 9, 1104 (2018).
Chmielewski, M. & Abken, H. TRUCKs: the fourth generation of CARs. Expert Opin. Biol. Ther. 15, 1145–1154 (2015).
Pang, Y., Hou, X., Yang, C., Liu, Y. & Jiang, G. Advances on chimeric antigen receptor-modified T-cell therapy for oncotherapy. Mol. Cancer 17, 91 (2018).
Salmikangas, P., Kinsella, N. & Chamberlain, P. Chimeric antigen receptor T-cells (CAR T-Cells) for cancer immunotherapy - moving target for industry? Pharm. Res. 35, 152 (2018).
Scheuermann, R. H. & Racila, E. CD19 antigen in leukemia and lymphoma diagnosis and immunotherapy. Leuk. Lymphoma 18, 385–397 (1995).
Morgan, R. A. et al. Case report of a serious adverse event following the administration of T cells transduced with a chimeric antigen receptor recognizing ERBB2. Mol. Ther. 18, 843–851 (2010).
Gacerez, A. T., Arellano, B. & Sentman, C. L. How chimeric antigen receptor design affects adoptive T cell therapy. J. Cell. Physiol. 231, 2590–2598 (2016).
Chan, C. J. et al. DNAM-1/CD155 interactions promote cytokine and NK cell-mediated suppression of poorly immunogenic melanoma metastases. J. Immunol. 184, 902–911 (2010).
Kim, J. S. et al. Cd226(-/-) natural killer cells fail to establish stable contacts with cancer cells and show impaired control of tumor metastasis in vivo. Oncoimmunology 6, e1338994 (2017).
Cappel, C. et al. Cytotoxic potential of IL-15-activated cytokine-induced killer cells against human neuroblastoma cells. Pediatr. Blood Cancer 63, 2230–2239 (2016).
Martinet, L. et al. DNAM-1 expression marks an alternative program of NK cell maturation. Cell Rep. 11, 85–97 (2015).
Rosskopf, S. et al. A Jurkat 76 based triple parameter reporter system to evaluate TCR functions and adoptive T cell strategies. Oncotarget 9, 17608–17619 (2018).
Sanchez-Correa, B. et al. Decreased expression of DNAM-1 on NK cells from acute myeloid leukemia patients. Immunol. Cell Biol. 90, 109–115 (2012).
Sun, S., Hao, H., Yang, G., Zhang, Y. & Fu, Y. Immunotherapy with CAR-modified T cells: toxicities and overcoming strategies. J. Immunol. Res. 2018, 2386187 (2018).
Sentman, M. L. et al. Mechanisms of acute toxicity in NKG2D chimeric antigen receptor T cell-treated mice. J. Immunol. 197, 4674–4685 (2016).
Morisaki, T., Onishi, H. & Katano, M. Cancer immunotherapy using NKG2D and DNAM-1 systems. Anticancer Res. 32, 2241–2247 (2012).
Lee, A., Sun, S., Sandler, A. & Hoang, T. Recent progress in therapeutic antibodies for cancer immunotherapy. Curr. Opin. Chem. Biol. 44, 56–65 (2018).
Niu, C. et al. Low-dose bortezomib increases the expression of NKG2D and DNAM-1 ligands and enhances induced NK and gammadelta T cell-mediated lysis in multiple myeloma. Oncotarget 8, 5954–5964 (2017).
Lopez-Cobo, S. et al. Impaired NK cell recognition of vemurafenib-treated melanoma cells is overcome by simultaneous application of histone deacetylase inhibitors. Oncoimmunology 7, e1392426 (2018).
Kamran, N. et al. Toll-like receptor ligands induce expression of the costimulatory molecule CD155 on antigen-presenting cells. PLoS ONE 8, e54406 (2013).
Yamashita-Kanemaru, Y. et al. CD155 (PVR/Necl-5) mediates a costimulatory signal in CD4+T cells and regulates allergic inflammation. J. Immunol. 194, 5644–5653 (2015).
Maier, M. K. et al. The adhesion receptor CD155 determines the magnitude of humoral immune responses against orally ingested antigens. Eur. J. Immunol. 37, 2214–2225 (2007).
Tahara-Hanaoka, S. et al. Functional characterization of DNAM-1 (CD226) interaction with its ligands PVR (CD155) and nectin-2 (PRR-2/CD112). Int. Immunol. 16, 533–538 (2004).
Oshima, T. et al. Nectin-2 is a potential target for antibody therapy of breast and ovarian cancers. Mol. Cancer 12, 60 (2013).
Liu, J. et al. Crystal structure of cell adhesion molecule nectin-2/CD112 and its binding to immune receptor DNAM-1/CD226. J. Immunol. 188, 5511–5520 (2012).
Seth, S. et al. Intranodal interaction with dendritic cells dynamically regulates surface expression of the co-stimulatory receptor CD226 protein on murine T cells. J. Biol. Chem. 286, 39153–39163 (2011).
Stamm, H. et al. Immune checkpoints PVR and PVRL2 are prognostic markers in AML and their blockade represents a new therapeutic option. Oncogene (2018). https://doi.org/10.1038/s41388-018-0288-y.
Morimoto, K. et al. Interaction of cancer cells with platelets mediated by Necl-5/poliovirus receptor enhances cancer cell metastasis to the lungs. Oncogene 27, 264–273 (2008).
Nasiri, H., Valedkarimi, Z., Aghebati-Maleki, L. & Majidi, J. Antibody-drug conjugates: promising and efficient tools for targeted cancer therapy. J. Cell. Physiol. 233, 6441–6457 (2018).
American Association for Cancer Research. Targeting Nectin-4 in bladder cancer. Cancer Discov. 7, OF3 (2017). https://doi.org/10.1158/2159-8290.CD-NB2017-095.
Challita-Eid, P. M. et al. Enfortumab Vedotin antibody-drug conjugate targeting Nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res. 76, 3003–3013 (2016).
Acknowledgements
S.J. is supported by the grant “Strengthening the capacity of CerVirVac for research in virus immunology and vaccinology”, KK.01.1.1.01.0006, awarded to the Scientific Centre of Excellence for Virus Immunology and Vaccines and co-financed by the European Regional Development Fund. P.K.B. and T.L.R. are supported by the Croatian Science Foundation (HRZZ) under project number 1533.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Competing interests
S.J., O.M. and P.T. are shareholders in Nectin Therapeutics Ltd. The remaining authors declare no competing interests.
Additional information
Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Kučan Brlić, P., Lenac Roviš, T., Cinamon, G. et al. Targeting PVR (CD155) and its receptors in anti-tumor therapy. Cell Mol Immunol 16, 40–52 (2019). https://doi.org/10.1038/s41423-018-0168-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41423-018-0168-y
Keywords
This article is cited by
-
Targeting TIGIT for cancer immunotherapy: recent advances and future directions
Biomarker Research (2024)
-
SPDYC serves as a prognostic biomarker related to lipid metabolism and the immune microenvironment in breast cancer
Immunologic Research (2024)
-
PVR (CD155) epigenetic status mediates immunotherapy response in multiple myeloma
Leukemia (2024)
-
The role of bone marrow microenvironment (BMM) cells in acute myeloid leukemia (AML) progression: immune checkpoints, metabolic checkpoints, and signaling pathways
Cell Communication and Signaling (2023)
-
CDK4/6 inhibitors and the pRB-E2F1 axis suppress PVR and PD-L1 expression in triple-negative breast cancer
Oncogenesis (2023)