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Original Research

CIITA-related block of HLA class II expression, upregulation of HLA class I, and heterogeneous expression of immune checkpoints in hepatocarcinomas: implications for new therapeutic approaches

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Article: 1548243 | Received 26 Jul 2018, Accepted 11 Nov 2018, Published online: 26 Nov 2018

References

  • WHO IARC. 2012.http://globocan.iarc.fr.
  • Ulahannan SV, Duffy AG, McNeel TS, Kish JK, Dickie LA, Rahma OE, McGlynn KA, Greten TF, Altekruse SF. Earlier presentation and application of curative treatments in hepatocellular carcinoma. Hepatology. 2014;60:1637–1644. doi:10.1002/hep.27288.
  • Cheng AL, Guan Z, Chen Z, Tsao CJ, Qin S, Kim JS, Yang TS, Tak WY, Pan H, Yu S, et al. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: subset analyses of the phase III Sorafenib Asia-Pacific trial. Eur J Cancer. 2012;48:1452–1465. doi:10.1016/j.ejca.2011.12.006.
  • Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015;348:56–61. doi:10.1126/science.aaa8172.
  • Greten TF, Wang XW, Korangy F. Current concepts of immune based treatments for patients with HCC: from basic science to novel treatment approaches. Gut. 2015;64:842–848. doi:10.1136/gutjnl-2014-307990.
  • Kudo M. Immune checkpoint inhibition in hepatocellular carcinoma: basics and ongoing clinical trials. Oncology. 2017;92:50–62. doi:10.1159/000451016.
  • Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39:1–10. doi:10.1016/j.immuni.2013.07.012.
  • Chen J, Jiang CC, Jin L, Zhang XD. Regulation of PD-L1: a novel role of pro-survival signalling in cancer. Annals Oncol. 2016;27:409–416. doi:10.1093/annonc/mdv615.
  • Wang Q, Liu F, Liu L. Prognostic significance of PD-L1 in solid tumor: an updated meta-analysis. Medicine (Baltimore). 2017;96: e6369. doi:10.1097/MD.0000000000006369
  • Shi F, Shi M, Zeng Z, Qi RZ, Liu ZW, Zhang JY, Yang YP, Tien P, Wang FS. PD-1 and PD-L1 upregulation promotes CD81 T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients. Int J Cancer. 2011;128:887–896. doi:10.1002/ijc.25397.
  • Gao Q, Wang X-Y, Qiu S-J, Yamato I, Sho M, Nakajima Y, Zhou J, Li B-Z, Shi Y-H, Xiao Y-S, et al. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res. 2009;15. doi:10.1158/1078-0432.CCR-09-0547.
  • Calderaro J, Rousseau B, Amaddeo G, Mercey M, Charpy C, Costentin C, Luciani A, Zafrani ES, Laurent A, Azoulay D, et al. Programmed Death Ligand 1 expression in hepatocellular carcinoma: relationship with clinical and pathological features. Hepatology. 2016;64:2038–2046. doi:10.1002/hep.28710.
  • Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–2454. doi:10.1056/NEJMoa1200690.
  • Germain RN, Margulies DH. The biochemistry and cellular biology of antigen processing and presentation. Annu Rev Immunol. 1993;11:403–450. doi:10.1146/annurev.iy.11.040193.002155.
  • Pardoll DM, Topalian SL. The role of CD4+ T cell responses in anti-tumor immunity. Curr Opin Immunol. 1998;10:588–594. doi:10.1016/S0952-7915(1098)80228-80228.
  • Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll DM, Levitsky H. The central role of CD4+ T cells in the antitumor immune response. J Exp Med. 1998;188:2357–2368.
  • Boon T, Cerottini JC, Van Den Eynde B, Van der Bruggen P, Van Pel A. Tumor antigens recognized by T lymphocytes. Annu Rev Immunol. 1994;12:337–365. doi:10.1146/annurev.iy.1112.040194.002005.
  • Accolla RS, Scarpellino L, Carra G, Guardiola J. Trans-acting element(s) operating across species barriers positively regulate the expression of major histocompatibility complex class II genes. J Exp Med. 1985;162:1117–1133.
  • Accolla RS, Jotterand-Bellomo M, Scarpellino L, Maffei A, Carra G, Guardiola J. Air-1, a newly found locus on mouse chromosome 16 encoding a trans-acting activator factor for MHC class II gene expression. J Exp Med. 1986;164:369–374.
  • Steimle V, Otten LA, Zufferey M, Mach B. Complementation cloning of an MHC class II transactivator mutated in hereditary MHC class II deficiency (or Bare Lymphocyte Syndrome). Cell. 1993;75:135–146.
  • Accolla RS, Lombardo L, Abdallah R, Raval G, Forlani G, Tosi G. Boosting the MHC class II-restricted tumor antigen presentation to CD4+ T helper cells: a critical issue for triggering protective immunity and re-orienting the tumor microenvironment toward an anti-tumor state. Frontiers Oncol. 2014;4:32. doi:10.3389/fonc.2014.00032.
  • Cabrera T, Ruiz-Cabello F, Garrido F. Biological implication of HLA-DR expression in tumors. Scand J Immunol. 1995;41(398):406. doi:10.1111/j.1365-3083.1995.tb03584.x.
  • Samuels S, Spaans VM, Osse M, Peters LA, Kenter GG, Fleuren GJ, Jordanova ES. Human Leukocyte Antigen-DR Expression is significantly related to an increased disease-free and disease-specific survival in patients with cervical adenocarcinoma. Int J Gynecol Cancer. 2016;26:1503–1509. doi:10.1097/IGC.0000000000000783.
  • Shi B, Vinyals A, Alia P, Broceño C, Chen F, Adrover M, Gelpi C, Price JE, Fabra A. Differential expression of MHC class II molecules in highly metastatic breast cancer cells is mediated by the regulation of the CIITA transcription Implication of CIITA in tumor and metastasis development. Int J Biochem Cell Biol. 2006;38:544–562. doi:10.1016/j.biocel.2005.07.012.
  • Del Campo AB, Carretero J, Aptsiauri N, Garrido F. Targeting HLA class I expression to increase tumor immunogenicity. Tissue Antigens. 2112;79:147–154. doi:10.1111/j.1399-0039.2011.01831.x.
  • Paterson AC, Sciot R, Kew MC, Callea F, Dusheiko GM, Desmet VJ. HLA expression in human hepatocellular carcinoma. Br J Cancer. 1988;57:369–373.
  • Sung CH, Hu CP, Hsu HC, Ng AK, Chou CK, Ting LP, Su TS, Han SH, Chang CM. Expression of class I and class II major histocompatibility antigens on human hepatocellular carcinoma. J Clin Invest. 1989;83:421–429. doi:10.1172/JCI113900.
  • Muhlethaler-Mottet A, Di Berardino W, Otten LA, Mach B. Activation of the MHC Class II Transactivator CIITA by Interferon-γ Requires Cooperative Interaction between Stat1 and USF-1. Immunity. 1998;8:157–166.
  • Strnad P, Paschke S, Jang KH, Ku NO. Keratins: markers and modulators of liver disease. Curr Opin Gastroenterol. 2012;28:209–216. doi:10.1097/MOG.0b013e3283525cb8.
  • Allard WJ, Matera J, Miller MC, Repollet M, Connelly MC, Rao C, Tibbe AG, Uhr JW, Terstappen LW. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin Cancer Res. 2004;10:6897–6904. doi:10.1158/1078-0432.CCR-04-0378.
  • Gottfried E, Kunz‐Schughart LA, Weber A, Rehli M, Peuker A, Müller A, Kastenberger M, Brockhoff G, Andreesen R, Kreutz M. Expression of CD68 in non‐myeloid cell types. Scand J Immunol. 2008;67:453–463. doi:10.1111/j.1365-3083.2008.02091.x.
  • The human protein atlas. http://www.proteinatlas.org/ENSG00000129226-CD68/cancer.
  • Scupoli MT, Sartoris S, Tosi G, Ennas MG, Nicolis M, Cestari T, Zamboni G, Martignoni G, Lemoine NR, Scarpa A, et al. Expression of MHC class I and class II antigens in pancreatic adenocarcinomas. Tissue Antigens. 1996;48:301–311.
  • Garrido F, Aptsiauri N, Doorduijn EM, Garcia Lora AM, van Hall T. The urgent need to recover MHC class I in cancers for effective immunotherapy. Curr Opin Immunol. 2016;39:44–51. doi:10.1016/j.coi.2015.12.007.
  • Park J, Thomas S, Munster PN. Epigenetic modulation with histone deacetylase inhibitors in combination with immunotherapy. Epigenomics. 2015;7:641–652. doi:10.2217/epi.15.16.
  • Johnson DB, Estrada MV, Salgado R, Sanchez V, Doxie DB, Opalenik SR, Vilgelm AE, Feld E, Johnson AS, Greenplate AR, et al. Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy. Nat Commun. 2016;7. doi:10.1038/ncomms10582.
  • Sconocchia G, Eppenberger-Castori S, Zlobec I, Karamitopoulou E, Arriga R, Coppola A, Caratelli S, Spagnoli GC, Lauro D, Lugli A, et al. HLA class II antigen expression in colorectal carcinoma tumors as a favorable prognostic marker. Neoplasia (New York, NY). 2014;16:31–42. doi:10.1593/neo.131568.
  • Steimle V, Siegrist C, Mottet A, Lisowska-Grospierre B, Mach B. Regulation of MHC class II expression by interferon-gamma mediated by the transactivator gene CIITA. Science. 1994;265:106–109.
  • Rigaud G, De Lerma Barbaro A, Nicolis M, Cestari T, Ramarli D, Riviera AP, Accolla RS. Induction of CIITA and modification of in vivo HLA-DR promoter occupancy in normal thymic epithelial cells treated with IFN-gamma: similarities and distinctions with respect to HLA-DR-constitutive B cells. J Immunol. 1996;156:4254–4258.
  • Accolla RS, De Lerma Barbaro A, Mazza S, Casoli C, De Maria A, Tosi G. The MHC class II transactivator: prey and hunter in infectious diseases. Trends Immunol. 2001;22:560–563. doi:10.1016/S1471-4906(01)02003-8.
  • Morris AC, Spangler WE, Boss JM. Methylation of class II trans-activator promoter IV: a novel mechanism of MHC class II gene control. J Immunol. 2000;164:4143–4149.
  • Radosevich M, Song Z, Gorga JC, Ksander B, Ono SJ. Epigenetic silencing of the CIITA gene and posttranscriptional regulation of class II MHC genes in ocular melanoma cells. Invest Ophthalmol Vis Sci. 2004;45:3185–3195. doi:10.1167/iovs.04-0111.
  • Meazza R, Comes A, Orengo AM, Ferrini S, Accolla RS. Tumor rejection by gene transfer of the MHC class II transactivator in murine mammary adenocarcinoma cells. Eur J Immunol. 2003;33:1183–1192. doi:10.1158/1078-0432.CCR-1106-0165.
  • Mortara L, Castellani P, Meazza R, Tosi G, De Lerma Barbaro A, Procopio FA, Comes A, Zardi L, Ferrini S, Accolla RS. CIITA-induced MHC class II expression in mammary adenocarcinoma leads to a Th1 polarization of the tumor microenvironment, tumor rejection, and specific antitumor memory. Clin Cancer Res. 2006;12:3435–3443. doi:10.1158/1078-0432.CCR-06-0165.
  • Frangione V, Mortara L, Castellani P, De Lerma Barbaro A, Accolla RS. CIITA-driven MHC-II positive tumor cells: preventive vaccines and superior generators of anti-tumor CD4+ T lymphocytes for immunotherapy. Int J Cancer. 2010;127:1614–1624. doi:10.1002/ijc.25183.
  • Ekkirala CR, Cappello P, Accolla RS, Giovarelli M, Romero I, Garrido C, Garcia-Lora AM, Novelli F. Class II transactivator-induced MHC class II expression in pancreatic cancer cells leads to tumor rejection and a specific antitumor memory response. Pancreas. 2014;43:1066–1072. doi:10.1097/MPA.0000000000000160.
  • Bou Nasser Eddine F, Forlani G, Lombardo L, Tedeschi A, Tosi G, Accolla RS. CIITA-driven MHC class II expressing tumor cells can efficiently prime naive CD4+ TH cells in vivo and vaccinate the host against parental MHC-II-negative tumor cell. Oncoimmunology. 2017. doi:10.1080/2162402X.2016.1261777.
  • Sartoris S, Valle MT, De Lerma Barbaro A, Tosi G, Cestari T, D’Agostino A, Megiovanni AM, Manca F, Accolla RS. HLA class II expression in uninducible hepatocarcinoma cells after trasfection of the AIR-1 gene product CIITA. Acquisition of antigen processing and presentation capacity. J Immunol. 1998;161:814–820.
  • Bou Nasser Eddine F, Ramia E, Tosi G, Forlani G, Accolla RS. Tumor Immunology meets…Immunology: modified cancer cells as professional APC for priming naïve tumor-specific CD4+ T cells. Oncoimmunology. 2017;6:e1356149. doi:10.1080/2162402X.2017.1356149.
  • Herkel J, Jagemann B, Wiegard C, Lazaro JF, Lueth S, Kanzler S, Blessing M, Schmitt E, Lohse AW. MHC class II-expressing hepatocytes function as antigen-presenting cells and activate specific CD4 T lymphocytes. Hepatology. 2003;37:1079–1085. doi:10.1053/jhep.2003.50191.
  • Hepavac cancer vaccine development for hepatocellular carcinoma. http://www.hepavac.eu.
  • Crispe IN. Hepatic T cells and liver tolerance. Nat Rev Immunol. 2003;3:51–62. doi:10.1038/nri981.
  • Makarova-Rusher OV, Medina-Echeverz J, Duffy AG, Greten TF. The yin and yang of evasion and immune activation in HCC. J Hepatol. 2015;62:1420–1429. doi:10.1016/j.jhep.2015.02.038.
  • Protzer U, Maini MK, Knolle PA. Living in the liver: hepatic infections. Nat Rev Immunol. 2012;12:201–213. doi:10.1038/nri3169.
  • Theise ND, Curado MP, Franceschi S, Hytiroglou P, Kudo M, Park YN, Sakamoto M, Torbenson M, Wee A. Hepatocellular carcinoma. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO classification of tumours of the digestive system. Geneva (Switzerland): WHO Press; 2010. 4th ed. p. 205–216.
  • Chiaravalli AM, Longhi E, Vigetti D, De Stefano FI, Deleonibus S, Capella C, Solcia E, Parravicini C. Gastrointestinal cancers reactive for the PAb416 antibody against JCV/SV40 T-Ag lack JCV DNA sequences while showing a distinctive pathologic profile. J Clin Pathol. 2012;66:44. doi:10.1136/jclinpath-2012-200963.
  • Forlani G, Abdallah R, Accolla RS, Tosi G. The major histocompatibility complex class II transactivator CIITA inhibits the persistent activation of NF-κB by the Human T Cell Lymphotropic Virus Type 1 Tax-1 Oncoprotein. J Virol. 2016;90:3708–3721. doi:10.1128/JVI.03000-15.
  • Tosi G, Forlani G, Andresen V, Turci M, Bertazzoni U, Franchini G. Major histocompatibility complex class II transactivator CIITA is a viral restriction factor that targets human T-cell lymphotropic virus type 1 Tax-1 function and inhibits viral replication. J Virol. 2011;85. doi:10.1128/JVI.00813-11.
  • Raval GU, Bidoia C, Forlani G, Tosi G, Gessain A, Accolla RS. Localization, quantification and interaction with host factors of endogenous HTLV-1 HBZ protein in infected cells and ATL. Retrovirology. 2015;12:59. doi:10.1186/s12977-015-0186-0.
  • Forlani G, Turrini F, Ghezzi S, Tedeschi A, Poli G, Accolla RS, Tosi G. The MHC-II transactivator CIITA inhibits Tat function and HIV-1 replication in human myeloid cells. J Transl Med. 2016;14:94. doi:10.1186/s12967-016-0867-z.
  • Li LC, Dahiya R. MethPrimer: designing primers for methylation PCRs. Bioinformatics. 2002;11:1427–1431. doi:10.1093/bioinformatics/18.11.1427.

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