{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:29:47Z","timestamp":1784042987599,"version":"3.55.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T00:00:00Z","timestamp":1584057600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T00:00:00Z","timestamp":1584057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"published-print":{"date-parts":[[2020,7]]},"DOI":"10.1007\/s00262-019-02465-y","type":"journal-article","created":{"date-parts":[[2020,3,13]],"date-time":"2020-03-13T10:07:19Z","timestamp":1584094039000},"page":"1253-1263","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Differential expression of Tim-3, PD-1, and CCR5 on peripheral T and B lymphocytes in hepatitis C virus-related hepatocellular carcinoma and their impact on treatment outcomes"],"prefix":"10.1007","volume":"69","author":[{"given":"Asmaa M.","family":"Zahran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8541-7304","authenticated-orcid":false,"given":"Helal F.","family":"Hetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Rayan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeer Sharaf","family":"Eldin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elham Ahmed","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein","family":"Fakhry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Soliman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omnia","family":"El-Badawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,13]]},"reference":[{"issue":"(Supplement_4)","key":"2465_CR1","first-page":"mdz155.055","volume":"30","author":"A Rayan","year":"2019","unstructured":"Rayan A, Zahran A, El-Badawy O, Soliman A (2019) P-056 Differential expression of CCR5, TIM3 and PD-1 on peripheral blood T and B lymphocytes from hepatitis C patients with hepatocellular carcinoma and their impact on treatment outcomes. Ann Oncol 30((Supplement_4)):mdz155.055","journal-title":"Ann Oncol"},{"issue":"Suppl 3","key":"2465_CR2","doi-asserted-by":"publisher","first-page":"S206","DOI":"10.1016\/s1590-8658(10)60507-5","volume":"42","author":"H Nordenstedt","year":"2010","unstructured":"Nordenstedt H, White DL, El-Serag HB (2010) The changing pattern of epidemiology in hepatocellular carcinoma. Dig Liver Dis 42(Suppl 3):S206\u2013214. https:\/\/doi.org\/10.1016\/s1590-8658(10)60507-5","journal-title":"Dig Liver Dis"},{"issue":"7529","key":"2465_CR3","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1038\/516S2a","volume":"516","author":"L Laursen","year":"2014","unstructured":"Laursen L (2014) A preventable cancer. Nature 516(7529):S2\u20133. https:\/\/doi.org\/10.1038\/516S2a","journal-title":"Nature"},{"issue":"1","key":"2465_CR4","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1080\/0284186X.2019.1657940","volume":"59","author":"AM Zahran","year":"2020","unstructured":"Zahran AM, Abdel-Rahim MH, Refaat A, Sayed M, Othman MM, Khalak LMR, Hetta HF (2020) Circulating hematopoietic stem cells, endothelial progenitor cells and cancer stem cells in hepatocellular carcinoma patients: contribution to diagnosis and prognosis. Acta Oncol 59(1):33\u201339","journal-title":"Acta Oncol"},{"key":"2465_CR5","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.micpath.2019.01.004","volume":"128","author":"VK Chaturvedi","year":"2019","unstructured":"Chaturvedi VK, Singh A, Dubey SK, Hetta HF, John J, Singh M (2019) Molecular mechanistic insight of hepatitis B virus mediated hepatocellular carcinoma. Microb Pathog 128:184\u2013194","journal-title":"Microb Pathog"},{"issue":"5","key":"2465_CR6","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1111\/j.1365-2893.2004.00521.x","volume":"11","author":"M Anzola","year":"2004","unstructured":"Anzola M (2004) Hepatocellular carcinoma: role of hepatitis B and hepatitis C viruses proteins in hepatocarcinogenesis. J Viral Hepatitis 11(5):383\u2013393. https:\/\/doi.org\/10.1111\/j.1365-2893.2004.00521.x","journal-title":"J Viral Hepatitis"},{"issue":"8","key":"2465_CR7","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1099\/jmm.0.000272","volume":"65","author":"HF Hetta","year":"2016","unstructured":"Hetta HF, Mekky MA, Khalil NK, Mohamed WA, El-Feky MA, Ahmed SH, Daef EA, Medhat A, Nassar MI, Sherman KE (2016) Extra-hepatic infection of hepatitis C virus in the colon tissue and its relationship with hepatitis C virus pathogenesis. J Med Microbiol 65(8):703","journal-title":"J Med Microbiol"},{"key":"2465_CR8","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1016\/j.humimm.2019.03.014","volume":"80","author":"AM Zahran","year":"2019","unstructured":"Zahran AM, Nafady-Hego H, Mansor SG, Abbas WA, Abdel-Malek MO, Mekky MA, Hetta HF (2019) Increased frequency and FOXP3 expression of human CD8+ CD25High+ T lymphocytes and its relation to CD4 regulatory T cells in patients with hepatocellular carcinoma. Hum Immunol 80:510\u2013516","journal-title":"Hum Immunol"},{"key":"2465_CR9","first-page":"69","volume":"26","author":"EA Hassan","year":"2019","unstructured":"Hassan EA, Ahmed EH, Nafee AM, El-Gafary N, Hetta HF, El-Mokhtar MA (2019) Regulatory T cells, IL10 and IL6 in HCV related hepatocellular carcinoma after transarterial chemoembolization (TACE). Egypt J Immunol 26:69\u201378","journal-title":"Egypt J Immunol"},{"key":"2465_CR10","first-page":"45","volume":"25","author":"AM Zahran","year":"2018","unstructured":"Zahran AM, Ashmawy AM, Rayan A, Elkady A, Elsherbiny NM, Hetta HF (2018) Frequency and implications of natural killer and natural killer T cells in hepatocellular carcinoma. Egypt J Immunol 25:45","journal-title":"Egypt J Immunol"},{"issue":"11","key":"2465_CR11","doi-asserted-by":"publisher","first-page":"e161","DOI":"10.1038\/cti.2017.47","volume":"6","author":"CL Elsegood","year":"2017","unstructured":"Elsegood CL, Tirnitz-Parker JE, Olynyk JK, Yeoh GC (2017) Immune checkpoint inhibition: prospects for prevention and therapy of hepatocellular carcinoma. Clin Transl Immunol 6(11):e161. https:\/\/doi.org\/10.1038\/cti.2017.47","journal-title":"Clin Transl Immunol"},{"issue":"8","key":"2465_CR12","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1038\/cmi.2017.35","volume":"14","author":"A Sarvaria","year":"2017","unstructured":"Sarvaria A, Madrigal JA, Saudemont A (2017) B cell regulation in cancer and anti-tumor immunity. Cell Mol Immunol 14(8):662","journal-title":"Cell Mol Immunol"},{"issue":"2","key":"2465_CR13","doi-asserted-by":"publisher","first-page":"00136","DOI":"10.15406\/ghoa.2016.05.00136","volume":"5","author":"H Hetta","year":"2016","unstructured":"Hetta H, Elkady A, Tohamy T, Badary M (2016) Regulatory B cells: key players in hepatocellular carcinoma progression. Gastroenterol Hepatol Open Access 5(2):00136","journal-title":"Gastroenterol Hepatol Open Access"},{"issue":"7","key":"2465_CR14","doi-asserted-by":"publisher","first-page":"e25443","DOI":"10.4161\/onci.25443","volume":"2","author":"C Fremd","year":"2013","unstructured":"Fremd C, Schuetz F, Sohn C, Beckhove P, Domschke C (2013) B cell-regulated immune responses in tumor models and cancer patients. Oncoimmunology 2(7):e25443. https:\/\/doi.org\/10.4161\/onci.25443","journal-title":"Oncoimmunology"},{"issue":"15","key":"2465_CR15","doi-asserted-by":"publisher","first-page":"7741","DOI":"10.1158\/0008-5472.can-05-3766","volume":"66","author":"S Inoue","year":"2006","unstructured":"Inoue S, Leitner WW, Golding B, Scott D (2006) Inhibitory effects of B cells on antitumor immunity. Can Res 66(15):7741\u20137747. https:\/\/doi.org\/10.1158\/0008-5472.can-05-3766","journal-title":"Can Res"},{"issue":"26","key":"2465_CR16","doi-asserted-by":"publisher","first-page":"10662","DOI":"10.1073\/pnas.1100994108","volume":"108","author":"T Schioppa","year":"2011","unstructured":"Schioppa T, Moore R, Thompson RG, Rosser EC, Kulbe H, Nedospasov S, Mauri C, Coussens LM, Balkwill FR (2011) B regulatory cells and the tumor-promoting actions of TNF-alpha during squamous carcinogenesis. Proc Natl Acad Sci USA 108(26):10662\u201310667. https:\/\/doi.org\/10.1073\/pnas.1100994108","journal-title":"Proc Natl Acad Sci USA"},{"issue":"7","key":"2465_CR17","doi-asserted-by":"publisher","first-page":"4006","DOI":"10.4049\/jimmunol.0903009","volume":"184","author":"DJ DiLillo","year":"2010","unstructured":"DiLillo DJ, Yanaba K, Tedder TF (2010) B cells are required for optimal CD4+ and CD8+ T cell tumor immunity: therapeutic B cell depletion enhances B16 melanoma growth in mice. J Immunol (Baltimore, Md : 1950) 184(7):4006\u20134016. https:\/\/doi.org\/10.4049\/jimmunol.0903009","journal-title":"J Immunol (Baltimore, Md : 1950)"},{"issue":"5","key":"2465_CR18","doi-asserted-by":"publisher","first-page":"3195","DOI":"10.4049\/jimmunol.0803773","volume":"183","author":"Q Li","year":"2009","unstructured":"Li Q, Teitz-Tennenbaum S, Donald EJ, Li M, Chang AE (2009) In vivo sensitized and in vitro activated B cells mediate tumor regression in cancer adoptive immunotherapy. J Immunol (Baltimore, Md : 1950) 183(5):3195\u20133203. https:\/\/doi.org\/10.4049\/jimmunol.0803773","journal-title":"J Immunol (Baltimore, Md : 1950)"},{"key":"2465_CR19","doi-asserted-by":"publisher","first-page":"19","DOI":"10.2147\/cmar.s111673","volume":"9","author":"A Raufi","year":"2017","unstructured":"Raufi A, Tirona MT (2017) Prospect of the use of checkpoint inhibitors in hepatocellular cancer treatments. Cancer Manag Res 9:19\u201327. https:\/\/doi.org\/10.2147\/cmar.s111673","journal-title":"Cancer Manag Res"},{"issue":"7","key":"2465_CR20","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1002\/jmv.25428","volume":"91","author":"HF Hetta","year":"2019","unstructured":"Hetta HF, Zahran AM, Mansor SG, Abdel-Malek MO, Mekky MA, Abbas WA (2019) Frequency and implications of myeloid-derived suppressor cells and lymphocyte subsets in Egyptian patients with hepatitis C virus-related hepatocellular carcinoma. J Med Virol 91(7):1319\u20131328","journal-title":"J Med Virol"},{"issue":"2\u20133","key":"2465_CR21","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/s12026-019-09075-x","volume":"67","author":"AM Zahran","year":"2019","unstructured":"Zahran AM, Zahran ZAM, El-Badawy O, Abdel-Rahim MH, Ali WA, Rayan A, El-Masry MA, Abozaid MA, Hetta HF (2019) Prognostic impact of toll-like receptors 2 and 4 expression on monocytes in Egyptian patients with hepatocellular carcinoma. Immunol Res\u00a067(2\u20133):157\u2013165. https:\/\/doi.org\/10.1007\/s12026-019-09075-x","journal-title":"Immunol Res"},{"issue":"3","key":"2465_CR22","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.20546\/ijcmas.2017.603.225","volume":"6","author":"HF Hetta","year":"2017","unstructured":"Hetta HF, Khairy H, Ismail S (2017) Circulating IL17A and IFN-gamma serum levels in cirrhotic hepatitis C virus infected patients with autoimmune thyroiditis. Int J Curr Microbiol Appl Sci 6(3):1972\u20131983","journal-title":"Int J Curr Microbiol Appl Sci"},{"issue":"10","key":"2465_CR23","doi-asserted-by":"publisher","first-page":"1390","DOI":"10.4254\/wjh.v7.i10.1390","volume":"7","author":"CM Liang","year":"2015","unstructured":"Liang CM, Chen L, Hu H, Ma HY, Gao LL, Qin J, Zhong CP (2015) Chemokines and their receptors play important roles in the development of hepatocellular carcinoma. World J Hepatol 7(10):1390\u20131402. https:\/\/doi.org\/10.4254\/wjh.v7.i10.1390","journal-title":"World J Hepatol"},{"issue":"5","key":"2465_CR24","doi-asserted-by":"publisher","first-page":"713","DOI":"10.3748\/wjg.14.713","volume":"14","author":"P Nahon","year":"2008","unstructured":"Nahon P, Sutton A, Rufat P, Simon C, Trinchet JC, Gattegno L, Beaugrand M, Charnaux N (2008) Chemokine system polymorphisms, survival and hepatocellular carcinoma occurrence in patients with hepatitis C virus-related cirrhosis. World J Gastroenterol 14(5):713\u2013719","journal-title":"World J Gastroenterol"},{"issue":"1","key":"2465_CR25","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1111\/imr.12520","volume":"276","author":"M Das","year":"2017","unstructured":"Das M, Zhu C, Kuchroo VK (2017) Tim-3 and its role in regulating anti-tumor immunity. Immunol Rev 276(1):97\u2013111. https:\/\/doi.org\/10.1111\/imr.12520","journal-title":"Immunol Rev"},{"issue":"5","key":"2465_CR26","doi-asserted-by":"publisher","first-page":"1776","DOI":"10.1002\/hep.27246","volume":"60","author":"T Hato","year":"2014","unstructured":"Hato T, Goyal L, Greten TF, Duda DG, Zhu AX (2014) Immune checkpoint blockade in hepatocellular carcinoma: current progress and future directions. Hepatology (Baltimore, MD) 60(5):1776\u20131782. https:\/\/doi.org\/10.1002\/hep.27246","journal-title":"Hepatology (Baltimore, MD)"},{"key":"2465_CR27","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1146\/annurev.immunol.26.021607.090331","volume":"26","author":"ME Keir","year":"2008","unstructured":"Keir ME, Butte MJ, Freeman GJ, Sharpe AH (2008) PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 26:677\u2013704. https:\/\/doi.org\/10.1146\/annurev.immunol.26.021607.090331","journal-title":"Annu Rev Immunol"},{"issue":"3","key":"2465_CR28","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1093\/annonc\/mdv615","volume":"27","author":"J Chen","year":"2016","unstructured":"Chen J, Jiang CC, Jin L, Zhang XD (2016) Regulation of PD-L1: a novel role of pro-survival signalling in cancer. Ann Oncol 27(3):409\u2013416. https:\/\/doi.org\/10.1093\/annonc\/mdv615","journal-title":"Ann Oncol"},{"issue":"3","key":"2465_CR29","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1002\/1521-4141(200203)32:3%3c634::aid-immu634%3e3.0.co;2-9","volume":"32","author":"L Carter","year":"2002","unstructured":"Carter L, Fouser LA, Jussif J, Fitz L, Deng B, Wood CR, Collins M, Honjo T, Freeman GJ, Carreno BM (2002) PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2. Eur J Immunol 32(3):634\u2013643. https:\/\/doi.org\/10.1002\/1521-4141(200203)32:3%3c634:aid-immu634%3e3.0.co;2-9","journal-title":"Eur J Immunol"},{"issue":"7","key":"2465_CR30","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1084\/jem.192.7.1027","volume":"192","author":"GJ Freeman","year":"2000","unstructured":"Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192(7):1027\u20131034. https:\/\/doi.org\/10.1084\/jem.192.7.1027","journal-title":"J Exp Med"},{"issue":"4","key":"2465_CR31","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1007\/s00262-004-0593-x","volume":"54","author":"C Blank","year":"2005","unstructured":"Blank C, Gajewski TF, Mackensen A (2005) Interaction of PD-L1 on tumor cells with PD-1 on tumor-specific T cells as a mechanism of immune evasion: implications for tumor immunotherapy. Cancer Immunol Immunother 54(4):307\u2013314. https:\/\/doi.org\/10.1007\/s00262-004-0593-x","journal-title":"Cancer Immunol Immunother"},{"issue":"1","key":"2465_CR32","doi-asserted-by":"publisher","first-page":"6","DOI":"10.2478\/ii-2018-0012","volume":"7","author":"Y Liu","year":"2018","unstructured":"Liu Y (2018) Immunomodulatory effects of Tim-3 and PD-1 on chronic hepatitis B virus infection. Infect Int 7(1):6\u201311","journal-title":"Infect Int"},{"key":"2465_CR33","doi-asserted-by":"publisher","first-page":"22","DOI":"10.20517\/2394-5079.2018.72","volume":"4","author":"G Missale","year":"2018","unstructured":"Missale G, Cariani E (2018) Time for hepatocellular carcinoma immunotherapy: insights for successful clinical applications in this challenging tumor. Hepatoma Res 4:22. https:\/\/doi.org\/10.20517\/2394-5079.2018.72","journal-title":"Hepatoma Res"},{"issue":"18","key":"2465_CR34","doi-asserted-by":"publisher","first-page":"9122","DOI":"10.1128\/JVI.00639-09","volume":"83","author":"L Golden-Mason","year":"2009","unstructured":"Golden-Mason L, Palmer BE, Kassam N, Townshend-Bulson L, Livingston S, McMahon BJ, Castelblanco N, Kuchroo V, Gretch DR, Rosen HR (2009) Negative immune regulator Tim-3 is overexpressed on T cells in hepatitis C virus infection and its blockade rescues dysfunctional CD4+ and CD8+ T cells. J Virol 83(18):9122\u20139130","journal-title":"J Virol"},{"issue":"1","key":"2465_CR35","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1186\/1743-422X-8-113","volume":"8","author":"W Wu","year":"2011","unstructured":"Wu W, Shi Y, Li J, Chen F, Chen Z, Zheng M (2011) Tim-3 expression on peripheral T cell subsets correlates with disease progression in hepatitis B infection. Virol J 8(1):113","journal-title":"Virol J"},{"issue":"3","key":"2465_CR36","doi-asserted-by":"publisher","first-page":"e15","DOI":"10.1038\/emi.2013.14","volume":"2","author":"J Schmidt","year":"2013","unstructured":"Schmidt J, Blum HE, Thimme R (2013) T-cell responses in hepatitis B and C virus infection: similarities and differences. Emerg Microbes Infect 2(3):e15. https:\/\/doi.org\/10.1038\/emi.2013.14","journal-title":"Emerg Microbes Infect"},{"issue":"4","key":"2465_CR37","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1002\/hep.25777","volume":"56","author":"H Li","year":"2012","unstructured":"Li H, Wu K, Tao K, Chen L, Zheng Q, Lu X, Liu J, Shi L, Liu C, Wang G, Zou W (2012) Tim-3\/galectin-9 signaling pathway mediates T-cell dysfunction and predicts poor prognosis in patients with hepatitis B virus-associated hepatocellular carcinoma. Hepatology (Baltimore, MD) 56(4):1342\u20131351. https:\/\/doi.org\/10.1002\/hep.25777","journal-title":"Hepatology (Baltimore, MD)"},{"issue":"4","key":"2465_CR38","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1002\/ijc.25397","volume":"128","author":"F Shi","year":"2011","unstructured":"Shi F, Shi M, Zeng Z, Qi RZ, Liu ZW, Zhang JY, Yang YP, Tien P, Wang FS (2011) PD-1 and PD-L1 upregulation promotes CD8(+) T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients. Int J Cancer 128(4):887\u2013896. https:\/\/doi.org\/10.1002\/ijc.25397","journal-title":"Int J Cancer"},{"issue":"1","key":"2465_CR39","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1186\/s13046-015-0256-0","volume":"34","author":"G He","year":"2015","unstructured":"He G, Zhang H, Zhou J, Wang B, Chen Y, Kong Y, Xie X, Wang X, Fei R, Wei L (2015) Peritumoural neutrophils negatively regulate adaptive immunity via the PD-L1\/PD-1 signalling pathway in hepatocellular carcinoma. J Exp Clin Cancer Res 34(1):141","journal-title":"J Exp Clin Cancer Res"},{"issue":"8","key":"2465_CR40","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1002\/bjs.1800600817","volume":"60","author":"RN Pugh","year":"1973","unstructured":"Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R (1973) Transection of the oesophagus for bleeding oesophageal varices. Br J Surg 60(8):646\u2013649","journal-title":"Br J Surg"},{"issue":"19","key":"2465_CR41","doi-asserted-by":"publisher","first-page":"5597","DOI":"10.1158\/0008-5472.can-16-0431","volume":"76","author":"P Tsou","year":"2016","unstructured":"Tsou P, Katayama H, Ostrin EJ, Hanash SM (2016) The emerging role of B cells in tumor immunity. Can Res 76(19):5597\u20135601. https:\/\/doi.org\/10.1158\/0008-5472.can-16-0431","journal-title":"Can Res"},{"issue":"9","key":"2465_CR42","doi-asserted-by":"publisher","first-page":"4977","DOI":"10.4049\/jimmunol.1001323","volume":"185","author":"BH Nelson","year":"2010","unstructured":"Nelson BH (2010) CD20+ B cells: the other tumor-infiltrating lymphocytes. J Immunol 185(9):4977\u20134982","journal-title":"J Immunol"},{"issue":"5","key":"2465_CR43","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1158\/2159-8290.cd-15-1408","volume":"6","author":"X Xiao","year":"2016","unstructured":"Xiao X, Lao XM, Chen MM, Liu RX, Wei Y, Ouyang FZ, Chen DP, Zhao XY, Zhao Q, Li XF, Liu CL, Zheng L, Kuang DM (2016) PD-1hi Identifies a novel regulatory B-cell population in human hepatoma that promotes disease progression. Cancer Discov 6(5):546\u2013559. https:\/\/doi.org\/10.1158\/2159-8290.cd-15-1408","journal-title":"Cancer Discov"},{"issue":"5","key":"2465_CR44","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.4049\/jimmunol.168.5.2225","volume":"168","author":"K Fukada","year":"2002","unstructured":"Fukada K, Sobao Y, Tomiyama H, Oka S, Takiguchi M (2002) Functional expression of the chemokine receptor CCR5 on virus epitope-specific memory and effector CD8+ T cells. J Immunol 168(5):2225\u20132232","journal-title":"J Immunol"},{"issue":"2","key":"2465_CR45","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1038\/84205","volume":"2","author":"SA Luther","year":"2001","unstructured":"Luther SA, Cyster JG (2001) Chemokines as regulators of T cell differentiation. Nat Immunol 2(2):102","journal-title":"Nat Immunol"},{"issue":"2","key":"2465_CR46","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.currproblcancer.2018.01.006","volume":"42","author":"A Butrym","year":"2018","unstructured":"Butrym A, Kryczek I, Dlubek D, Jaskula E, Lange A, Jurczyszyn A, Mazur G (2018) High expression of CC chemokine receptor 5 (CCR5) promotes disease progression in patients with B-cell non-Hodgkin lymphomas. Curr Probl Cancer 42(2):268\u2013275","journal-title":"Curr Probl Cancer"},{"issue":"6","key":"2465_CR47","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1111\/j.1572-0241.2004.30265.x","volume":"99","author":"Y Liu","year":"2004","unstructured":"Liu Y, Poon RT, Feng X, Yu WC, Luk JM, Fan ST (2004) Reduced expression of chemokine receptors on peripheral blood lymphocytes in patients with hepatocellular carcinoma. Am J Gastroenterol 99(6):1111\u20131121. https:\/\/doi.org\/10.1111\/j.1572-0241.2004.30265.x","journal-title":"Am J Gastroenterol"},{"issue":"2","key":"2465_CR48","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.clim.2004.10.006","volume":"114","author":"Y Liu","year":"2005","unstructured":"Liu Y, Poon RT, Hughes J, Feng X, Yu WC, Fan ST (2005) Chemokine receptors support infiltration of lymphocyte subpopulations in human hepatocellular carcinoma. Clin Immunol 114(2):174\u2013182","journal-title":"Clin Immunol"},{"issue":"1","key":"2465_CR49","doi-asserted-by":"publisher","first-page":"106","DOI":"10.4161\/onci.1.1.17995","volume":"1","author":"A Gonzalez-Martin","year":"2012","unstructured":"Gonzalez-Martin A, Mira E, Manes S (2012) CCR5 in cancer immunotherapy: More than an \u201cattractive\u201d receptor for T cells. Oncoimmunology 1(1):106\u2013108. https:\/\/doi.org\/10.4161\/onci.1.1.17995","journal-title":"Oncoimmunology"},{"issue":"2","key":"2465_CR50","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/S1473-3099(15)00424-7","volume":"16","author":"YY Liu","year":"2016","unstructured":"Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, Doi Y, Tian G, Dong B, Huang X, Yu LF, Gu D, Ren H, Chen X, Lv L, He D, Zhou H, Liang Z, Liu JH, Shen J (2016) Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis 16(2):161\u2013168. https:\/\/doi.org\/10.1016\/S1473-3099(15)00424-7","journal-title":"Lancet Infect Dis"},{"issue":"5","key":"2465_CR51","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1158\/2159-8290.CD-16-0307","volume":"6","author":"Z Ren","year":"2016","unstructured":"Ren Z, Peng H, Fu Y-X (2016) PD-1 shapes B cells as evildoers in the tumor microenvironment. Cancer Discov 6(5):477\u2013478","journal-title":"Cancer Discov"},{"issue":"4","key":"2465_CR52","doi-asserted-by":"publisher","first-page":"e23849","DOI":"10.4161\/onci.23849","volume":"2","author":"K Sakuishi","year":"2013","unstructured":"Sakuishi K, Ngiow SF, Sullivan JM, Teng MW, Kuchroo VK, Smyth MJ, Anderson AC (2013) TIM3(+)FOXP3(+) regulatory T cells are tissue-specific promoters of T-cell dysfunction in cancer. Oncoimmunology 2(4):e23849. https:\/\/doi.org\/10.4161\/onci.23849","journal-title":"Oncoimmunology"},{"key":"2465_CR53","volume-title":"Global hepatitis report 2017","author":"World Health Organization","year":"2017","unstructured":"World Health Organization (2017) Global hepatitis report 2017. World Health Organization, Washington"},{"issue":"1","key":"2465_CR54","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.clinre.2018.08.003","volume":"43","author":"MA Mekky","year":"2019","unstructured":"Mekky MA, Abdel-Malek MO, Osman HA, Abdel-Aziz EM, Hashim A-KA, Hetta HF, Morsy KH (2019) Efficacy of ombitasvir\/paritaprevir\/ritonavir\/ribavirin in management of HCV genotype 4 and end-stage kidney disease. Clin Res Hepatol Gastroenterol 43(1):82\u201387","journal-title":"Clin Res Hepatol Gastroenterol"},{"key":"2465_CR55","doi-asserted-by":"publisher","first-page":"273","DOI":"10.2147\/IDR.S181638","volume":"12","author":"MA Mekky","year":"2019","unstructured":"Mekky MA, Sayed HI, Abdelmalek MO, Saleh MA, Osman OA, Osman HA, Morsy KH, Hetta HF (2019) Prevalence and predictors of occult hepatitis C virus infection among Egyptian patients who achieved sustained virologic response to sofosbuvir\/daclatasvir therapy: a multi-center study. Infect Drug Resist 12:273","journal-title":"Infect Drug Resist"},{"issue":"2","key":"2465_CR56","doi-asserted-by":"publisher","first-page":"78","DOI":"10.3138\/canlivj.1.2.007","volume":"1","author":"S Mazouz","year":"2018","unstructured":"Mazouz S, Boisvert M, Shoukry NH, Lamarre D (2018) Reversing immune dysfunction and liver damage after direct-acting antiviral treatment for hepatitis C. Can Liver J 1(2):78\u2013105","journal-title":"Can Liver J"},{"issue":"4","key":"2465_CR57","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1089\/vim.2015.0093","volume":"29","author":"EA Abdel-Hameed","year":"2016","unstructured":"Abdel-Hameed EA, Rouster SD, Ji H, Ulm A, Hetta HF, Anwar N, Sherman KE, Shata MTM (2016) Evaluating the role of cellular immune responses in the emergence of HCV NS3 resistance mutations during protease inhibitor therapy. Viral Immunol 29(4):252\u2013258","journal-title":"Viral Immunol"},{"issue":"19","key":"2465_CR58","doi-asserted-by":"publisher","first-page":"31705","DOI":"10.18632\/oncotarget.15954","volume":"8","author":"Y Zhang","year":"2017","unstructured":"Zhang Y, Cai P, Liang T, Wang L, Hu L (2017) TIM-3 is a potential prognostic marker for patients with solid tumors: a systematic review and meta-analysis. Oncotarget 8(19):31705","journal-title":"Oncotarget"},{"issue":"3","key":"2465_CR59","doi-asserted-by":"publisher","first-page":"587","DOI":"10.3233\/CBM-181368","volume":"22","author":"AM Zahran","year":"2018","unstructured":"Zahran AM, Saleh M, Mostafa F, Sayed MM, Rayan A, Ali AM, Hetta HF (2018) Up-regulation of regulatory T cells, CD200 and TIM3 expression in cytogenetically normal acute myeloid leukemia. Cancer Biomarkers 22(3):587\u2013595","journal-title":"Cancer Biomarkers"},{"issue":"7593","key":"2465_CR60","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1038\/nature16969","volume":"531","author":"C Ma","year":"2016","unstructured":"Ma C, Kesarwala AH, Eggert T, Medina-Echeverz J, Kleiner DE, Jin P, Stroncek DF, Terabe M, Kapoor V, ElGindi M (2016) NAFLD causes selective CD4+ T lymphocyte loss and promotes hepatocarcinogenesis. Nature 531(7593):253","journal-title":"Nature"}],"container-title":["Cancer Immunology, Immunotherapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-019-02465-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00262-019-02465-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-019-02465-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,13]],"date-time":"2021-03-13T00:10:01Z","timestamp":1615594201000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00262-019-02465-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,13]]},"references-count":60,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["2465"],"URL":"https:\/\/doi.org\/10.1007\/s00262-019-02465-y","relation":{},"ISSN":["0340-7004","1432-0851"],"issn-type":[{"value":"0340-7004","type":"print"},{"value":"1432-0851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,13]]},"assertion":[{"value":"5 July 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 December 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 March 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"All authors declare that they have no conflict of interests<b>.<\/b>","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The research was done according to the ethical guidelines of the Declaration of Helsinki 1975 and was accepted by the local ethics committee of the Faculty of Medicine, Assiut University, Assiut, Egypt (IRB no: 17300300).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Written informed consent was obtained from all participants before inclusion in the study. Participants consented for the use of their specimens and data for research and publication.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}