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Immune response in cervical intraepithelial neoplasms

  • Priscila Thais Silva Mantoani1
  • Daniela Rodrigues Siqueira1
  • Millena Prata Jammal1
  • Eddie Fernando Candido Murta1
  • Rosekeila Simões Nomelini1,*,

1Department of Gynecology and Obstetrics, Research Institute of Oncology (IPON), Federal University of Triângulo Mineiro, 38025-440 Uberaba, Brazil

DOI: 10.31083/j.ejgo4205146 Vol.42,Issue 5,October 2021 pp.973-981

Submitted: 09 May 2021 Accepted: 20 July 2021

Published: 15 October 2021

(This article belongs to the Special Issue Immunology in Gynecological Cancer)

*Corresponding Author(s): Rosekeila Simões Nomelini E-mail: rosekeila@terra.com.br; rosekeila.nomelini@pesquisador.cnpq.br

Abstract

Objective: The current study aims perform a comprehensive overview of the topic immune response in cervical intraepithelial neoplasms, summarizing the findings of literature. Data sources: PubMed database. Methods of study selection: A search for the following descriptors was performed in the PubMed database: descriptor “immune response in cervical cancer and Human Papilloma Virus (HPV)”; “immunotherapy in premalignant cervical lesions”. Tabulation, integration and results: The articles identified were published between 1967 and 2021. We selected 85 articles for review on the subject (reference 16 onwards). This literature review shows the important role that the immune system plays in the development and progression of cervical cancer. Immune response in pre-neoplastic cervical lesions includes host defense mechanisms against the HPV, adaptive immunity and the function of cytokines. Predictive factors of viral persistence and progression of premalignant lesions may also be associated with immune response. Conclusion: One of the determining factors for the persistence or elimination of HPV infections and their evolution to pre-neoplastic lesions is the cellular immune response, as the progression or regression of the tumor depends on the type and amount of cytokines secreted by the body. The investigation of these immune reactions may provide new therapeutic targets for cervical intraepithelial neoplasms.


Keywords

Cervical intraepithelial neoplasms; Immune response; Cervical cancer; Human Papilloma Virus; Immunotherapy


Cite and Share

Priscila Thais Silva Mantoani,Daniela Rodrigues Siqueira,Millena Prata Jammal,Eddie Fernando Candido Murta,Rosekeila Simões Nomelini. Immune response in cervical intraepithelial neoplasms. European Journal of Gynaecological Oncology. 2021. 42(5);973-981.

References

[1] Nayar R, Wilbur DC. The Bethesda System for Reporting Cervical Cytology. Definitions, Criteria, and Explanatory Notes (pp. 321). 3rd edn. In Nayar R, Wilbur D. (eds.) Cham, Switzerland: Springer International Publishing. 2015.

[2] Instituto Nacional de Câncer (INCA). Incidência do Câncer no Brasil. 2020. Available at: https://www.inca.gov.br/controle-do-cancer-do-colo-do-utero/conceito-e-magnitude (Accessed: 15 November 2020).

[3] Leto MGP, Santos Júnior GF, Porro AM, Tomimori J. Human papillomavirus infection: etiopathogenesis, molecular biology and clinical manifestations. Journal Brazilian Annals of Dermatology. 2011; 86: 306–317.

[4] Münger K, Baldwin A, Edwards KM, Hayakawa H, Nguyen CL, Owens M, et al. Mechanisms of human papillomavirus-induced oncogenesis. Journal of Virology. 2004; 78: 11451–11460.

[5] Scheffner M, Werness BA, Huibregtse JM, Levine AJ, Howley PM. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell. 1990; 63: 1129–1136.

[6] zur Hausen H. Papillomavirus infections—a major cause of human cancers. Biochimica et Biophysica Acta. 1996; 1288: F55–F78.

[7] Muñoz N, Méndez F, Posso H, Molano M, van den Brule AJC, Ronderos M, et al. Incidence, duration, and determinants of cervical human papillomavirus infection in a cohort of Colombian women with normal cytological results. Journal of Infectious Diseases. 2004; 190: 2077–2087.

[8] Foldvari M. HPV infections: can they be eradicated using nanotechnology? Nanomedicine. 2012; 8: 131–135.

[9] Franceschi S, Herrero R, Clifford GM, Snijders PJF, Arslan A, Anh PTH, et al. Variations in the age-specific curves of human papillomavirus prevalence in women worldwide. International Journal of Cancer. 2006; 119: 2677–2684.

[10] Rodríguez AC, Schiffman M, Herrero R, Hildesheim A, Bratti C, Sherman ME, et al. Longitudinal study of human papillomavirus persistence and cervical intraepithelial neoplasia grade 2/3: critical role of duration of infection. Journal of the National Cancer Institute. 2010; 102: 315–324.

[11] Sarkola ME, Grénman SE, Rintala MAM, Syrjänen KJ, Syrjänen SM. Human papillomavirus in the placenta and umbilical cord blood. Acta Obstetricia et Gynecologica Scandinavica. 2008; 87: 1181–1188.

[12] Medeiros LR, Ethur ABDM, Hilgert JB, Zanini RR, Berwanger O, Bozzetti MC, et al. Vertical transmission of the human papillomavirus: a systematic quantitative review. Cadernos De SaúDe PúBlica. 2005; 21: 1006–1015.

[13] Ferenczy A, Bergeron C, Richart RM. Human papillomavirus DNA in fomites on objects used for the management of patients with genital human papillomavirus infections. Obstetrics and Gynecology. 1989; 74: 950–954.

[14] Roden RB, Kirnbauer R, Jenson AB, Lowy DR, Schiller JT. Interaction of papillomaviruses with the cell surface. Journal of Virology. 1994; 68: 7260–7266.

[15] Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International Journal of Cancer. 2015; 136: E359–E386.

[16] Westrich JA, Warren CJ, Pyeon D. Evasion of host immune defenses by human papillomavirus. Virus Research. 2017; 231: 21–33.

[17] Otani S, Fujii T, Kukimoto I, Yamamoto N, Tsukamoto T, Ichikawa R, et al. Cytokine expression profiles in cervical mucus from patients with cervical cancer and its precursor lesions. Cytokine. 2019; 120: 210–219.

[18] Amador-Molina A, Hernández-Valencia JF, Lamoyi E, Contreras-Paredes A, Lizano M. Role of innate immunity against human papillomavirus (HPV) infections and effect of adjuvants in promoting specific immune response. Viruses. 2013; 5: 2624–2642.

[19] Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. i. Definition according to profiles of lymphokine activities and secreted proteins. Journal of Immunology. 1986; 136: 2348–2357.

[20] Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S. Human papillomavirus and cervical cancer. Lancet. 2007; 370: 890–907.

[21] Stanley M. Pathology and epidemiology of HPV infection in females. Gynecologic Oncology. 2010; 117: S5–S10.

[22] Diamond MS, Farzan M. The broadspectrum antiviral functions of IFIT and IFITM proteins. Nature Reviews. Immunology. 2013; 13: 46–57.

[23] Schelhaas M, Shah B, Holzer M, Blattmann P, Kühling L, Day PM, et al. Entry of human papillomavirus type 16 by actindependent, clathrin- and lipid raft-independent endocytosis. PLoS Pathogens. 2012; 8: e1002657.

[24] DiGiuseppe S, Bienkowska-Haba M, Sapp M. Human Papillomavirus Entry: Hiding in a Bubble. Journal of Virology. 2016; 90: 8032–8035.

[25] Griffin LM, Cicchini L, Pyeon D. Human papillomavirus infection is inhibited by host autophagy in primary human keratinocytes. Virology. 2013; 437: 12–19.

[26] Pyeon D, Pearce SM, Lank SM, Ahlquist P, Lambert PF. Establishment of human papillomavirus infection requires cell cycle progression. PLOS Pathogens. 2009; 5: e1000318.

[27] Wiens ME, Smith JG. Alpha-defensin HD5 inhibits furin cleavage of human papillomavirus 16 L2 to block infection. Journal of Virology. 2015; 89: 2866–2874.

[28] Chan YK, Gack MU. Viral evasion of intracellular DNA and RNA sensing. Nature Reviews. Microbiology. 2016; 14: 360–373.

[29] Li X, Shu C, Yi G, Chaton CT, Shelton CL, Diao J, et al. Cyclic GMP-AMP synthase is activated by doublestranded DNA-induced oligomerization. Immunity. 2013; 39: 1019–1031.

[30] Reinholz M, Kawakami Y, Salzer S, Kreuter A, Dombrowski Y, Koglin S, et al. HPV16 activates the AIM2 inflammasome in keratinocytes. Archives of Dermatological Research. 2013; 305: 723–732.

[31] Lo Cigno I, De Andrea M, Borgogna C, Albertini S, Landini MM, Peretti A, et al. The Nuclear DNA Sensor IFI16 Acts as a Restriction Factor for Human Papillomavirus Replication through Epigenetic Modifications of the Viral Promoters. Journal of Virology. 2015; 89: 7506–7520.

[32] Daud II, Scott ME, Ma Y, Shiboski S, Farhat S, Moscicki A. Association between tolllike receptor expression and human papillomavirus type 16 persistence. International Journal of Cancer. 2011; 128: 879–886.

[33] Viscidi RP, Schiffman M, Hildesheim A, Herrero R, Castle PE, Bratti MC, et al. Seroreactivity to Human Papillomavirus (HPV) Types 16, 18, or 31 and Risk of Subsequent HPV Infection. Cancer Epidemiology Biomarkers & Prevention. 2004; 13: 324–327.

[34] Warren CJ, Van Doorslaer K, Pandey A, Espinosa JM, Pyeon D. Role of the host restriction factor APOBEC3 on papillomavirus evolution. Virus Evolution. 2015; 1: vev015.

[35] Bontkes HJ, Ruizendaal JJ, Kramer D, Meijer CJLM, Hooijberg E. Plasmacytoid dendritic cells are present in cervical carcinoma and become activated by human papillomavirus type 16 virus-like particles. Gynecologic Oncology. 2005; 96: 897–901.

[36] Orange JS. Natural killer cell deficiency. Journal of Allergy and Clinical Immunology. 2013; 132: 515–525.

[37] Woo YL, Sterling J, Damay I, Coleman N, Crawford R, van der Burg SH, et al. Characterising the local immune responses in cervical intraepithelial neoplasia: a cross-sectional and longitudinal analysis. BJOG: an International Journal of Obstetrics and Gynaecology. 2008; 115: 1616–1612.

[38] Da Silva DM, Woodham AW, Skeate JG, Rijkee LK, Taylor JR, Brand HE, et al. Langerhans cells from women with cervical precancerous lesions become functionally responsive against human papillomavirus after activation with stabilized Poly-i:C. Clinical Immunology. 2015; 161: 197–208.

[39] Handisurya A, Day PM, Thompson CD, Bonelli M, Lowy DR, Schiller JT. Strainspecific properties and T cells regulate the susceptibility to papilloma induction by Mus musculus papillomavirus 1. PLoS Pathogens. 2014; 10: e1004314.

[40] Uberoi A, Yoshida S, Frazer IH, Pitot HC, Lambert PF. Role of Ultraviolet Radiation in Papillomavirus-Induced Disease. PLoS Pathogens. 2016; 12: e1005664.

[41] Stanley MA. Epithelial cell responses to infection with human papillomavirus: results from a population-based study in Costa Rica. Clinical Microbiology Reviews. 2012; 25: 215–222.

[42] Evans M, Borysiewicz LK, Evans AS, Rowe M, Jones M, Gileadi U, et al. Antigen processing defects in cervical carcinomas limit the presentation of a CTL epitope from human papillomavirus 16 E6. Journal of Immunology. 2001; 167: 5420–5428.

[43] Patel S, Chiplunkar S. Host immune responses to cervical cancer. Current Opinion in Obstetrics & Gynecology. 2009; 21: 54–59.

[44] Zoodsma M, Nolte IM, Schipper M, Oosterom E, van der Steege G, de Vries EGE, et al. Interleukin-10 and Fas polymorphisms and susceptibility for (pre)neoplastic cervical disease. International Journal of Gynecological Cancer. 2005; 15: 282–290.

[45] Roman A, Munger K. The papillomavirus E7 proteins. Virology. 2013; 445: 138–168.

[46] Vande Pol SB, Klingelhutz AJ. Papillomavirus E6 oncoproteins. Virology. 2013; 445: 115–137.

[47] Vandermark ER, Deluca KA, Gardner CR, Marker DF, Schreiner CN, Strickland DA, et al. Human papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization. Virology. 2012; 425: 53–60.

[48] Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity. 2000; 12: 121–127.

[49] Schmitt E, Klein M, Bopp T. Th9 cells, new players in adaptive immunity. Trends in Immunology. 2014; 35: 61–68.

[50] Dudakov JA, Hanash AM, van den Brink MRM. Interleukin-22: immunobiology and pathology. Annual Review of Immunology. 2015; 33: 747–785.

[51] Lee GR. The Balance of Th17 versus Treg Cells in Autoimmunity. International Journal of Molecular Sciences. 2018; 19.

[52] Peghini BC, Abdalla DR, Barcelos ACM, Teodoro LDGVL, Murta EFC, Michelin MA. Local cytokine profiles of patients with cervical intraepithelial and invasive neoplasia. Human Immunology. 2012; 73: 920–926.

[53] Hiraoka N, Onozato K, Kosuge T, Hirohashi S. Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clinical Cancer Research. 2006; 12: 5423–5434.

[54] Fu J, Xu D, Liu Z, Shi M, Zhao P, Fu B, et al. Increased Regulatory T Cells Correlate with CD8 T-Cell Impairment and Poor Survival in Hepatocellular Carcinoma Patients. Gastroenterology. 2007; 132: 2328–2339.

[55] Gauza JE, Pimenta ATM, Moreira FV, Melli PPS, Quintana SM. IL-10 como preditor da progressão das lesões intraepiteliais do colo uterino: revisão da literatura. Arquivos Catarinenses de Medicina. 2013; 42: 92–97.

[56] Iwata T, Fujii T, Morii K, Saito M, Sugiyama J, Nishio H, et al. Cytokine profile in cervical mucosa of Japanese patients with cervical intraepithelial neoplasia. International Journal of Clinical Oncology. 2015; 20: 126–133.

[57] Tsukui T, Hildesheim A, Schiffman MH, Lucci J, Contois D, Lawler P, et al. Interleukin 2 production in vitro by peripheral lymphocytes in response to human papillomavirus-derived peptides: correlation with cervical pathology. Cancer Research. 1996; 56: 3967–3974.

[58] Tartour E, Gey A, Sastre-Garau X, Lombard Surin I, Mosseri V, Fridman WH. Prognostic value of intratumoral interferon gamma messenger RNA expression in invasive cervical carcinomas. Jour-nal of the National Cancer Institute. 1998; 90: 287–294.

[59] El-Sherif AM, Seth R, Tighe PJ, Jenkins D. Quantitative analysis of IL-10 and IFN-gamma mRNA levels in normal cervix and human papillomavirus type 16 associated cervical precancer. Journal of Pathology. 2001; 195: 179–185.

[60] Clerici M, Merola M, Ferrario E, Trabattoni D, Villa ML, Stefanon B, et al. Cytokine production patterns in cervical intraepithelial neoplasia: association with human papillomavirus infection. Journal of the National Cancer Institute. 1997; 89: 245–250.

[61] Stanley M. Immune responses to human papillomavirus. Vaccine. 2006; 24: S16–S22.

[62] Wang SS, Hildesheim A. Chapter 5: Viral and host factors in human papillomavirus persistence and progression. Journal of the National Cancer Institute. Monographs. 2003; 31: 35–40.

[63] Carrington M, Wang S, Martin MP, Gao X, Schiffman M, Cheng J, et al. Hierarchy of resistance to cervical neoplasia mediated by combinations of killer immunoglobulin-like receptor and human leukocyte antigen loci. Journal of Experimental Medicine. 2005; 201: 1069–1075.

[64] Goodman MT, Shvetsov YB, McDuffie K, Wilkens LR, Zhu X, Thompson PJ, et al. Prevalence, acquisition, and clearance of cervical human papillomavirus infection among women with normal cytology: Hawaii Human Papillomavirus Cohort Study. Cancer Research. 2008; 68: 8813–8824.

[65] Ylitalo N, Sørensen P, Josefsson AM, Magnusson PK, Andersen PK, Pontén J, et al. Consistent high viral load of human papillomavirus 16 and risk of cervical carcinoma in situ: a nested casecontrol study. Lancet. 2000; 355: 2194–2198.

[66] Josefsson AM, Magnusson PK, Ylitalo N, Sørensen P, Qwarforth-Tubbin P, Andersen PK, et al. Viral load of human papilloma virus 16 as a determinant for development of cervical carcinoma in situ: a nested casecontrol study. Lancet. 2000; 355: 2189–2193.

[67] Plummer M, Schiffman M, Castle P, Maucort‐Boulch D, Wheeler

C. A 2‐Year Prospective Study of Human Papillomavirus Persistence among Women with a Cytological Diagnosis of Atypi-cal Squamous Cells of Undetermined Significance or Low‐Grade Squamous Intraepithelial Lesion. Journal of Infectious Diseases. 2007; 195: 1582–1589.

[68] Schiffman M, Kjaer SK. Chapter 2: Natural history of anogenital human papillomavirus infection and neoplasia. Journal of the National Cancer Institute. Monographs. 2003; 14–19.

[69] Schiffman M, Herrero R, Desalle R, Hildesheim A, Wacholder S, Rodriguez AC, et al. The carcinogenicity of human papillomavirus types reflects viral evolution. Virology. 2005; 337: 76–84.

[70] Kjaer S, Høgdall E, Frederiksen K, Munk C, van den Brule A, Svare E, et al. The absolute risk of cervical abnormalities in hig-hrisk human papillomavirus-positive, cytologically normal women over a

10- year period. Cancer Research. 2006; 66: 10630–10636.

[71] Herrero R, Castle PE, Schiffman M, Bratti MC, Hildesheim A, Morales J, et al. Epidemiologic profile of typespecific human papillomavirus infection and cervical neoplasia in Guanacaste, Costa Rica. Journal of Infectious Diseases. 2005; 191: 1796–1807.

[72] Richardson H, Abrahamowicz M, Tellier P, Kelsall G, du Berger R, Ferenczy A, et al. Modifiable risk factors associated with clearance of type-specific cervical human papillomavirus infections in a cohort of university students. Cancer Epidemiology, Biomarkers & Prevention. 2005; 14: 1149–1156.

[73] Hogewoning CJA, Bleeker MCG, van den Brule AJC, Voorhorst FJ, Snijders PJF, Berkhof J, et al. Condom use promotes regression of cervical intraepithelial neoplasia and clearance of human papillomavirus: a randomized clinical trial. International Journal of Cancer. 2003; 107: 811–816.

[74] David E, Belot A, Lega JC, Durieu I, Rousset-Jablonski C. Papillo-mavirus humain et lupus érythémateux systémique. La Revue De MéDecine Interne. 2021; 42: 498–504. (In French)

[75] Penn I. Cancer is a complication of severe immunosuppression. Surgery, Gynecology & Obstetrics. 1986; 162: 603–610.

[76] Baccarani U. De novo malignancies after kidney and liver transplantation: experience on 582 consecutive cases. Transplantation Proceedings. 2006; 38: 1135–1137.

[77] Brown MR. HPV subtypes analysis in lower genital tract neoplasm of female renal transplantation recipients. Gynecologic Oncology. 2000; 79: 220–224.

[78] Harwood C. HPV infection and non-melanoma skin cancer in immunosuppressed and immunocompetent individuals. Journal of Medical Virology. 2000; 61: 289–297.

[79] Young JL, Jazaeri AA, Darus CJ, Modesitt SC. Cyclooxygenase-2 in cervical neoplasia: a review. Gynecologic Oncology. 2008; 109: 140–145.

[80] Grabosch SM, Shariff OM, Helm CW. Non-steroidal anti-inflammatory agents to induce regression and prevent the progression of cervical intraepithelial neoplasia. Cochrane Database of Systematic Reviews. 2018; 2: CD004121.

[81] Maher J, Davies ET. Targeting cytotoxic T lymphocytes for cancer immunotherapy. British Journal of Cancer. 2004; 91: 817–821.

[82] Hildesheim A, Herrero R, Wacholder S, Rodriguez AC, Solomon D, Bratti MC, et al. Effect of Human Papillomavirus 16/18 L1 Viruslike Particle Vaccine among Young Women with Preexisting Infection: a randomized trial. Journal of the American Medical Association. 2007; 298: 743–753.

[83] FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. New England Journal of Medicine. 2007; 356: 1915–1927.

[84] Cordeiro MN, De Lima RDCP, Paolini F, Melo ARDS, Campos APF, Venuti A, et al. Current research into novel therapeutic vaccines against cervical cancer. Expert Review of Anticancer Therapy. 2018; 18: 365–376.

[85] Maehama T, Nishio M, Otani J, Mak TW, Suzuki A. The role of Hippo‐YAP signaling in squamous cell carcinomas. Cancer Science. 2021; 112: 51–60.

[86] Santin AD, Bellone S, Palmieri M, Zanolini A, Ravaggi A, Siegel ER, et al. Human papillomavirus type 16 and 18 E7-pulsed dendritic cell vaccination of stage IB or IIA cervical cancer patients: a phase i escalating-dose trial. Journal of Virology. 2008; 82: 1968–1979.

[87] Rahma OE, Herrin VE, Ibrahim RA, Toubaji A, Bernstein S, Dakheel O, et al. Preimmature dendritic cells (PIDC) pulsed with HPV16 E6 or E7 peptide are capable of eliciting specific immune response in patients with advanced cervical cancer. Journal of Translational Medicine. 2014; 12: 353.

[88] Barra F, Della Corte L, Noberasco G, Foreste V, Riemma G, Di Filippo C, et al. Advances in therapeutic vaccines for treating human papillomavirus‐related cervical intraepithelial neoplasia. Journal of Obstetrics and Gynaecology Research. 2020; 46: 989–1006.

[89] Trimble CL, Morrow MP, Kraynyak KA, Shen X, Dallas M, Yan J, et al. Safety, efficacy, and immunogenicity of VGX-3100, a therapeutic synthetic DNA vaccine targeting human papillomavirus 16 and 18 E6 and E7 proteins for cervical intraepithelial neoplasia 2/3: a randomised, double-blind, placebo-controlled phase 2b trial. Lancet. 2015; 386: 2078–2088.

[90] Brun J, Rajaonarison J, Nocart N, Hoarau L, Brun S, Garrigue I. Targeted immunotherapy of high-grade cervical intra-epithelial neoplasia: Expectations from clinical trials. Molecular and Clinical Oncology. 2018; 8: 227–235.

[91] Di Tucci C, Schiavi MC, Faiano P, D’Oria O, Prata G, Sciuga V, et al. Therapeutic vaccines and immune checkpoints inhibition options for gynecological cancers. Critical Reviews in Oncology/Hematology. 2018; 128: 30–42.

[92] Schiller M, Metze D, Luger TA, Grabbe S, Gunzer M. Immune response modifiers–mode of action. Experimental Dermatology. 2006; 15: 331–341.

[93] Schön M, Schön MP. The antitumoral mode of action of imiquimod and other imidazoquinolines. Current Medicinal Chemistry. 2007; 14: 681–687.

[94] Grimm C, Polterauer S, Natter C, Rahhal J, Hefler L, Tempfer CB, et al. Treatment of cervical intraepithelial neoplasia with topical imiquimod: a randomized controlled trial. Obstetrics and Gynecology. 2012; 120: 152–159.

[95] de Witte CJ, van de Sande AJM, van Beekhuizen HJ, Koeneman MM, Kruse AJ, Gerestein CG. Imiquimod in cervical, vaginal and vulvar intraepithelial neoplasia: a review. Gynecologic Oncology. 2015; 139: 377–384.

[96] Nomelini RS, De Carvalho Mardegan M, Murta EFC. Utilization of Interferon in Gynecologic and Breast Cancer. Clinical Medicine. Oncology. 2007; 1: 111–120.

[97] Friedman RM. Interferon binding: the first step in establishment of antiviral activity. Science. 1967; 156: 1760–1761.

[98] Michelin MA, Montes L, Nomelini RS, Trovó MA, Murta EFC. Helper T lymphocyte response in the peripheral blood of patients with intraepithelial neoplasia submitted to immunotherapy with pegylated interferon-α. International Journal of Molecular Sciences. 2015; 16: 5497–5509.

[99] Ramos MC, Mardegan MC, Peghini BC, Adad SJ, Michelin MA, Murta EFC. Expression of cytokines in cervical stroma in patients with high-grade cervical intraepithelial neoplasia after treatment with intralesional interferon α-2b. European Journal of Gynaecological Oncology. 2010; 31: 522–529.

[100] Mundim FV, Trovó MA, Stark LM, Jammal MP, Michelin MA, Murta EFC. Pegylated-interferon-alpha treatment modifying T cell cytokine profile in tumor microenvironment of patients with cervical intraepitelial neoplasia. European Journal of Gynaecological Oncology. 2021; 42: 96–104.


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