Human Endogenous Retroviruses (HERVs): Shaping the Innate Immune Response in Cancers
Abstract
:1. Introduction
2. HERVs Expression: Interaction with the Innate Immune System
2.1. HERVs Are Silenced by Epigenetic Mechanisms at Steady State
2.2. HERVs Expression Is Modulated by the Immune Response, Microbiota and Viral Infections
2.3. Role of PRRs, TLR Signaling and B Cell Response in the Control of ERVs
2.4. HERVs as Network Regulator: the Example of the IFN-γ Network
3. HERVs as Modulators of the Innate Immune Response
3.1. Activation of Innate Immunity by HERV Nucleic Acids
3.2. Activation of Innate Immunity by HERV- Derived Proteins
3.3. Suppression of the Immune Response
4. HERVs as Innate “Adjuvants” in Cancer
4.1. Turning Cancerous Cells into Virus-Infected Cells
4.2. Impact of HERVs Expression in the Response to Immune Checkpoint Inhibitors
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Burns, K.H. Transposable elements in cancer. Nat. Rev. Cancer 2017, 17, 415–424. [Google Scholar] [CrossRef]
- Kassiotis, G.; Stoye, J.P. Immune responses to endogenous retroelements: Taking the bad with the good. Nat. Rev. Immunol. 2016, 16, 207–219. [Google Scholar] [CrossRef]
- Vargiu, L.; Rodriguez-Tomé, P.; Sperber, G.O.; Cadeddu, M.; Grandi, N.; Blikstad, V.; Tramontano, E.; Blomberg, J. Classification and characterization of human endogenous retroviruses; mosaic forms are common. Retrovirology 2016, 13, 7. [Google Scholar] [CrossRef] [Green Version]
- Kassiotis, G. Endogenous retroviruses and the development of cancer. J. Immunol. 2014, 192, 1343–1349. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rowe, H.M.; Trono, D. Dynamic control of endogenous retroviruses during development. Virology 2011, 411, 273–287. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dupressoir, A.; Lavialle, C.; Heidmann, T. From ancestral infectious retroviruses to bona fide cellular genes: Role of the captured syncytins in placentation. Placenta 2012, 33, 663–671. [Google Scholar] [CrossRef] [PubMed]
- Brattås, P.L.; Jönsson, M.E.; Fasching, L.; Nelander Wahlestedt, J.; Shahsavani, M.; Falk, R.; Falk, A.; Jern, P.; Parmar, M.; Jakobsson, J. TRIM28 controls a gene regulatory network based on endogenous retroviruses in human neural progenitor cells. Cell Rep. 2017, 18, 1–11. [Google Scholar] [CrossRef]
- Ashley, J.; Cordy, B.; Lucia, D.; Fradkin, L.G.; Budnik, V.; Thomson, T. Retrovirus-like gag protein arc1 binds RNA and traffics across synaptic boutons. Cell 2018, 172, 262–274.e11. [Google Scholar] [CrossRef] [Green Version]
- Jang, H.S.; Shah, N.M.; Du, A.Y.; Dailey, Z.Z.; Pehrsson, E.C.; Godoy, P.M.; Zhang, D.; Li, D.; Xing, X.; Kim, S.; et al. Transposable elements drive widespread expression of oncogenes in human cancers. Nat. Genet. 2019, 51, 611–617. [Google Scholar] [CrossRef]
- Chen, T.; Meng, Z.; Gan, Y.; Wang, X.; Xu, F.; Gu, Y.; Xu, X.; Tang, J.; Zhou, H.; Zhang, X.; et al. The viral oncogene Np9 acts as a critical molecular switch for co-activating β-catenin, ERK, Akt and Notch1 and promoting the growth of human leukemia stem/progenitor cells. Leukemia 2013, 27, 1469–1478. [Google Scholar] [CrossRef]
- Chiappinelli, K.B.; Strissel, P.L.; Desrichard, A.; Li, H.; Henke, C.; Akman, B.; Hein, A.; Rote, N.S.; Cope, L.M.; Snyder, A.; et al. Inhibiting DNA methylation causes an interferon response in cancer via dsrna including endogenous retroviruses. Cell 2015, 162, 974–986. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Roulois, D.; Loo Yau, H.; Singhania, R.; Wang, Y.; Danesh, A.; Shen, S.Y.; Han, H.; Liang, G.; Jones, P.A.; Pugh, T.J.; et al. DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Cell 2015, 162, 961–973. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bestor, T.H.; Tycko, B. Creation of genomic methylation patterns. Nat. Genet. 1996, 12, 363–367. [Google Scholar] [CrossRef] [PubMed]
- Collins, P.L.; Kyle, K.E.; Egawa, T.; Shinkai, Y.; Oltz, E.M. The histone methyltransferase SETDB1 represses endogenous and exogenous retroviruses in B lymphocytes. Proc. Natl. Acad. Sci. USA 2015, 112, 8367–8372. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Adoue, V.; Binet, B.; Malbec, A.; Fourquet, J.; Romagnoli, P.; van Meerwijk, J.P.M.; Amigorena, S.; Joffre, O.P. The histone methyltransferase setdb1 controls thelper Cell lineage integrity by repressing endogenous retroviruses. Immunity 2019, 50, 629–644.e8. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Martin, F.J.; Xu, Y.; Lohmann, F.; Ciccone, D.N.; Nicholson, T.B.; Loureiro, J.J.; Chen, T.; Huang, Q. KMT1E-mediated chromatin modifications at the FcγRIIb promoter regulate thymocyte development. Genes Immun. 2015, 16, 162–169. [Google Scholar] [CrossRef]
- Kato, M.; Takemoto, K.; Shinkai, Y. A somatic role for the histone methyltransferase Setdb1 in endogenous retrovirus silencing. Nat. Commun. 2018, 9, 1683. [Google Scholar] [CrossRef] [Green Version]
- Ishak, C.A.; Marshall, A.E.; Passos, D.T.; White, C.R.; Kim, S.J.; Cecchini, M.J.; Ferwati, S.; MacDonald, W.A.; Howlett, C.J.; Welch, I.D.; et al. An RB-EZH2 complex mediates silencing of repetitive DNA sequences. Mol. Cell 2016, 64, 1074–1087. [Google Scholar] [CrossRef] [Green Version]
- Stoye, J.P.; Moroni, C. Endogenous retrovirus expression in stimulated murine lymphocytes. Identification of a new locus controlling mitogen induction of a defective virus. J. Exp. Med. 1983, 157, 1660–1674. [Google Scholar] [CrossRef] [Green Version]
- Young, G.R.; Mavrommatis, B.; Kassiotis, G. Microarray analysis reveals global modulation of endogenous retroelement transcription by microbes. Retrovirology 2014, 11, 59. [Google Scholar] [CrossRef] [Green Version]
- Yu, P.; Lübben, W.; Slomka, H.; Gebler, J.; Konert, M.; Cai, C.; Neubrandt, L.; Prazeres da Costa, O.; Paul, S.; Dehnert, S.; et al. Nucleic acid-sensing Toll-like receptors are essential for the control of endogenous retrovirus viremia and ERV-induced tumors. Immunity 2012, 37, 867–879. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Contreras-Galindo, R.; Kaplan, M.H.; Markovitz, D.M.; Lorenzo, E.; Yamamura, Y. Detection of HERV-K(HML-2) viral RNA in plasma of HIV type 1-infected individuals. AIDS Res. Hum. Retroviruses 2006, 22, 979–984. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Contreras-Galindo, R.; López, P.; Vélez, R.; Yamamura, Y. HIV-1 infection increases the expression of human endogenous retroviruses type K (HERV-K) in vitro. AIDS Res. Hum. Retroviruses 2007, 23, 116–122. [Google Scholar] [CrossRef] [Green Version]
- Hung, T.; Pratt, G.A.; Sundararaman, B.; Townsend, M.J.; Chaivorapol, C.; Bhangale, T.; Graham, R.R.; Ortmann, W.; Criswell, L.A.; Yeo, G.W.; et al. The Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression. Science 2015, 350, 455–459. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stauffer, Y.; Marguerat, S.; Meylan, F.; Ucla, C.; Sutkowski, N.; Huber, B.; Pelet, T.; Conrad, B. Interferon-α-induced endogenous superantigen: A model linking environment and autoimmunity. Immunity 2001, 15, 591–601. [Google Scholar] [CrossRef] [Green Version]
- Cañadas, I.; Thummalapalli, R.; Kim, J.W.; Kitajima, S.; Jenkins, R.W.; Christensen, C.L.; Campisi, M.; Kuang, Y.; Zhang, Y.; Gjini, E.; et al. Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses. Nat. Med. 2018, 24, 1143–1150. [Google Scholar] [CrossRef] [PubMed]
- Everett, R.D.; Boutell, C.; Hale, B.G. Interplay between viruses and host sumoylation pathways. Nat. Rev. Microbiol. 2013, 11, 400–411. [Google Scholar] [CrossRef] [PubMed]
- Hu, M.-M.; Liao, C.-Y.; Yang, Q.; Xie, X.-Q.; Shu, H.-B. Innate immunity to RNA virus is regulated by temporal and reversible sumoylation of RIG-I and MDA5. J. Exp. Med. 2017, 214, 973–989. [Google Scholar] [CrossRef] [Green Version]
- Lee, A.; CingÖz, O.; Sabo, Y.; Goff, S.P. Characterization of interaction between Trim28 and YY1 in silencing proviral DNA of Moloney murine leukemia virus. Virology 2018, 516, 165–175. [Google Scholar] [CrossRef]
- Schmidt, N.; Domingues, P.; Golebiowski, F.; Patzina, C.; Tatham, M.H.; Hay, R.T.; Hale, B.G. An influenza virus-triggered SUMO switch orchestrates co-opted endogenous retroviruses to stimulate host antiviral immunity. PNAS 2019, 116, 17399–17408. [Google Scholar] [CrossRef] [Green Version]
- Young, G.R.; Eksmond, U.; Salcedo, R.; Alexopoulou, L.; Stoye, J.P.; Kassiotis, G. Resurrection of endogenous retroviruses in antibody-deficient mice. Nature 2012, 491, 774–778. [Google Scholar] [CrossRef] [PubMed]
- Browne, E.P. Toll-like receptor 7 controls the anti-retroviral germinal center response. PLoS Pathog. 2011, 7, e1002293. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kane, M.; Case, L.K.; Wang, C.; Yurkovetskiy, L.; Dikiy, S.; Golovkina, T.V. Innate immune sensing of retroviral infection via Toll-like receptor 7 occurs upon viral entry. Immunity 2011, 35, 135–145. [Google Scholar] [CrossRef] [Green Version]
- Hurst, T.P.; Aswad, A.; Karamitros, T.; Katzourakis, A.; Smith, A.L.; Magiorkinis, G. Interferon-inducible protein 16 (IFI16) has a broad-spectrum binding ability against ssdna targets: An evolutionary hypothesis for antiretroviral checkpoint. Front. Microbiol. 2019, 10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Feschotte, C. Transposable elements and the evolution of regulatory networks. Nat. Rev. Genet. 2008, 9, 397–405. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chuong, E.B.; Elde, N.C.; Feschotte, C. Regulatory evolution of innate immunity through co-option of endogenous retroviruses. Science 2016, 351, 1083–1087. [Google Scholar] [CrossRef] [Green Version]
- Lynch, V.J. A copy-and-paste gene regulatory network. Science 2016, 351, 1029–1030. [Google Scholar] [CrossRef]
- Barbalat, R.; Ewald, S.E.; Mouchess, M.L.; Barton, G.M. Nucleic acid recognition by the innate immune system. Annu. Rev. Immunol. 2011, 29, 185–214. [Google Scholar] [CrossRef]
- Iwasaki, A.; Medzhitov, R. Control of adaptive immunity by the innate immune system. Nat. Immunol. 2015, 16, 343–353. [Google Scholar] [CrossRef]
- Heil, F.; Hemmi, H.; Hochrein, H.; Ampenberger, F.; Kirschning, C.; Akira, S.; Lipford, G.; Wagner, H.; Bauer, S. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 2004, 303, 1526–1529. [Google Scholar] [CrossRef] [Green Version]
- Gao, D.; Wu, J.; Wu, Y.-T.; Du, F.; Aroh, C.; Yan, N.; Sun, L.; Chen, Z.J. Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. Science 2013, 341, 903–906. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Takaoka, A.; Wang, Z.; Choi, M.K.; Yanai, H.; Negishi, H.; Ban, T.; Lu, Y.; Miyagishi, M.; Kodama, T.; Honda, K.; et al. DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature 2007, 448, 501–505. [Google Scholar] [CrossRef] [PubMed]
- Rigby, R.E.; Webb, L.M.; Mackenzie, K.J.; Li, Y.; Leitch, A.; Reijns, M.A.M.; Lundie, R.J.; Revuelta, A.; Davidson, D.J.; Diebold, S.; et al. RNA:DNA hybrids are a novel molecular pattern sensed by TLR9. EMBO J. 2014, 33, 542–558. [Google Scholar] [CrossRef] [PubMed]
- Stetson, D.B.; Ko, J.S.; Heidmann, T.; Medzhitov, R. Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell 2008, 134, 587–598. [Google Scholar] [CrossRef] [Green Version]
- Wheeler, L.A.; Trifonova, R.T.; Vrbanac, V.; Barteneva, N.S.; Liu, X.; Bollman, B.; Onofrey, L.; Mulik, S.; Ranjbar, S.; Luster, A.D.; et al. TREX1 knockdown induces an interferon response to HIV that delays viral infection in humanized mice. Cell Rep. 2016, 15, 1715–1727. [Google Scholar] [CrossRef] [Green Version]
- Nazli, A.; Kafka, J.K.; Ferreira, V.H.; Anipindi, V.; Mueller, K.; Osborne, B.J.; Dizzell, S.; Chauvin, S.; Mian, M.F.; Ouellet, M.; et al. HIV-1 gp120 induces TLR2-and TLR4-mediated innate immune activation in human female genital epithelium. J. Immunol. 2013, 191, 4246–4258. [Google Scholar] [CrossRef]
- Rolland, A.; Jouvin-Marche, E.; Viret, C.; Faure, M.; Perron, H.; Marche, P.N. The envelope protein of a human endogenous retrovirus-W family activates innate immunity through CD14/TLR4 and promotes th1-like responses. J. Immunol. 2006, 176, 7636–7644. [Google Scholar] [CrossRef]
- Antony, J.M.; van Marle, G.; Opii, W.; Butterfield, D.A.; Mallet, F.; Yong, V.W.; Wallace, J.L.; Deacon, R.M.; Warren, K.; Power, C. Human endogenous retrovirus glycoprotein–mediated induction of redox reactants causes oligodendrocyte death and demyelination. Nat. Neurosci. 2004, 7, 1088–1095. [Google Scholar] [CrossRef]
- Rosenberg, N.; Jolicoeur, P. Retroviral pathogenesis. In Retroviruses; Coffin, J.M., Hughes, S.H., Varmus, H.E., Eds.; Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY, USA, 1997; ISBN 978-0-87969-571-2. [Google Scholar]
- Mangeney, M.; Renard, M.; Schlecht-Louf, G.; Bouallaga, I.; Heidmann, O.; Letzelter, C.; Richaud, A.; Ducos, B.; Heidmann, T. Placental syncytins: Genetic disjunction between the fusogenic and immunosuppressive activity of retroviral envelope proteins. Proc. Natl. Acad. Sci. USA 2007, 104, 20534–20539. [Google Scholar] [CrossRef] [Green Version]
- Denner, J. The transmembrane proteins contribute to immunodeficiencies induced by HIV-1 and other retroviruses. AIDS 2014, 28, 1081–1090. [Google Scholar] [CrossRef]
- Denner, J. Expression and function of endogenous retroviruses in the placenta. APMIS 2016, 124, 31–43. [Google Scholar] [CrossRef] [PubMed]
- Morozov, V.A.; Thi, V.L.D.; Denner, J. The transmembrane protein of the human endogenous retrovirus—K (HERV-K) modulates cytokine release and gene expression. PLoS ONE 2013, 8, e70399. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ferrari, L.; Cafora, M.; Rota, F.; Hoxha, M.; Iodice, S.; Tarantini, L.; Dolci, M.; Delbue, S.; Pistocchi, A.; Bollati, V. Extracellular vesicles released by colorectal cancer cell lines modulate innate immune response in zebrafish model: The possible role of human endogenous retroviruses. Int. J. Mol. Sci. 2019, 20, 3669. [Google Scholar] [CrossRef] [Green Version]
- Hummel, J.; Kämmerer, U.; Müller, N.; Avota, E.; Schneider-Schaulies, S. Human endogenous retrovirus envelope proteins target dendritic cells to suppress T-cell activation. Eur. J. Immunol. 2015, 45, 1748–1759. [Google Scholar] [CrossRef]
- Jaenisch, R.; Schnieke, A.; Harbers, K. Treatment of mice with 5-azacytidine efficiently activates silent retroviral genomes in different tissues. Proc. Natl. Acad. Sci. USA 1985, 82, 1451–1455. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, H.; Chiappinelli, K.B.; Guzzetta, A.A.; Easwaran, H.; Yen, R.-W.C.; Vatapalli, R.; Topper, M.J.; Luo, J.; Connolly, R.M.; Azad, N.S.; et al. Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers. Oncotarget 2014, 5, 587–598. [Google Scholar] [CrossRef] [PubMed]
- Chiappinelli, K.B.; Zahnow, C.A.; Ahuja, N.; Baylin, S.B. Combining epigenetic and immunotherapy to combat cancer. Cancer Res. 2016, 76, 1683–1689. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Besch, R.; Poeck, H.; Hohenauer, T.; Senft, D.; Häcker, G.; Berking, C.; Hornung, V.; Endres, S.; Ruzicka, T.; Rothenfusser, S.; et al. Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon-independent apoptosis in human melanoma cells. J. Clin. Investig. 2009, 119, 2399–2411. [Google Scholar] [CrossRef] [Green Version]
- Tobiasson, M.; Abdulkadir, H.; Lennartsson, A.; Katayama, S.; Marabita, F.; De Paepe, A.; Karimi, M.; Krjutskov, K.; Einarsdottir, E.; Grövdal, M.; et al. Comprehensive mapping of the effects of azacitidine on DNA methylation, repressive/permissive histone marks and gene expression in primary cells from patients with MDS and MDS-related disease. Oncotarget 2017, 8, 28812–28825. [Google Scholar] [CrossRef]
- Krug, B.; De Jay, N.; Harutyunyan, A.S.; Deshmukh, S.; Marchione, D.M.; Guilhamon, P.; Bertrand, K.C.; Mikael, L.G.; McConechy, M.K.; Chen, C.C.L.; et al. Pervasive H3K27 acetylation leads to ERV expression and a therapeutic vulnerability in H3K27M gliomas. Cancer Cell 2019, 36, 338–339. [Google Scholar] [CrossRef]
- Sheng, W.; LaFleur, M.W.; Nguyen, T.H.; Chen, S.; Chakravarthy, A.; Conway, J.R.; Li, Y.; Chen, H.; Yang, H.; Hsu, P.-H.; et al. Lsd1 ablation stimulates anti-tumor immunity and enables checkpoint blockade. Cell 2018, 174, 549–563. [Google Scholar] [CrossRef] [PubMed]
- Goel, S.; DeCristo, M.J.; Watt, A.C.; BrinJones, H.; Sceneay, J.; Li, B.B.; Khan, N.; Ubellacker, J.M.; Xie, S.; Metzger-Filho, O.; et al. CDK4/6 inhibition triggers anti-tumour immunity. Nature 2017, 548, 471–475. [Google Scholar] [CrossRef] [PubMed]
- Bonaventura, P.; Shekarian, T.; Alcazer, V.; Valladeau-Guilemond, J.; Valsesia-Wittmann, S.; Amigorena, S.; Caux, C.; Depil, S. Cold tumors: A therapeutic challenge for immunotherapy. Front. Immunol. 2019, 10, 168. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Smith, C.C.; Beckermann, K.E.; Bortone, D.S.; De Cubas, A.A.; Bixby, L.M.; Lee, S.J.; Panda, A.; Ganesan, S.; Bhanot, G.; Wallen, E.M.; et al. Endogenous retroviral signatures predict immunotherapy response in clear cell renal cell carcinoma. J. Clin. Investig. 2018, 128, 4804–4820. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Heidegger, S.; Wintges, A.; Stritzke, F.; Bek, S.; Steiger, K.; Koenig, P.-A.; Göttert, S.; Engleitner, T.; Öllinger, R.; Nedelko, T.; et al. RIG-I activation is critical for responsiveness to checkpoint blockade. Sci. Immunol. 2019, 4, eaau8943. [Google Scholar] [CrossRef]
- Leruste, A.; Tosello, J.; Ramos, R.N.; Tauziède-Espariat, A.; Brohard, S.; Han, Z.-Y.; Beccaria, K.; Andrianteranagna, M.; Caudana, P.; Nikolic, J.; et al. Clonally expanded T cells reveal immunogenicity of rhabdoid tumors. Cancer Cell 2019, 36, 597–612. [Google Scholar] [CrossRef]
- Wang-Johanning, F.; Frost, A.R.; Johanning, G.L.; Khazaeli, M.B.; LoBuglio, A.F.; Shaw, D.R.; Strong, T.V. Expression of human endogenous retrovirus k envelope transcripts in human breast cancer. Clin. Cancer Res. 2001, 7, 1553–1560. [Google Scholar]
- Rycaj, K.; Plummer, J.B.; Yin, B.; Li, M.; Garza, J.; Radvanyi, L.; Ramondetta, L.M.; Lin, K.; Johanning, G.L.; Tang, D.G.; et al. Cytotoxicity of human endogenous retrovirus K-specific T cells toward autologous ovarian cancer cells. Clin. Cancer Res. 2015, 21, 471–483. [Google Scholar] [CrossRef] [Green Version]
- Krishnamurthy, J.; Rabinovich, B.A.; Mi, T.; Switzer, K.C.; Olivares, S.; Maiti, S.N.; Plummer, J.B.; Singh, H.; Kumaresan, P.R.; Huls, H.M.; et al. Genetic engineering of T cells to target herv-K, an ancient retrovirus on melanoma. Clin. Cancer Res. 2015, 21, 3241–3251. [Google Scholar] [CrossRef] [Green Version]
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Alcazer, V.; Bonaventura, P.; Depil, S. Human Endogenous Retroviruses (HERVs): Shaping the Innate Immune Response in Cancers. Cancers 2020, 12, 610. https://doi.org/10.3390/cancers12030610
Alcazer V, Bonaventura P, Depil S. Human Endogenous Retroviruses (HERVs): Shaping the Innate Immune Response in Cancers. Cancers. 2020; 12(3):610. https://doi.org/10.3390/cancers12030610
Chicago/Turabian StyleAlcazer, Vincent, Paola Bonaventura, and Stephane Depil. 2020. "Human Endogenous Retroviruses (HERVs): Shaping the Innate Immune Response in Cancers" Cancers 12, no. 3: 610. https://doi.org/10.3390/cancers12030610