Analyze Diet
Cells2020; 9(11); 2364; doi: 10.3390/cells9112364

Equine Penile Squamous Cell Carcinomas as a Model for Human Disease: A Preliminary Investigation on Tumor Immune Microenvironment.

Abstract: Penile squamous cell carcinomas (SCCs) are common tumors in older horses, with poor prognosis mostly due to local invasion and recurrence. These tumors are thought to be mainly caused by papillomavirus type 2 (EcPV-2). The aim of this study is to characterize the tumor immune environment (TIME) in equine penile tumors. Equine penile epithelial tumors (17 epSCCs; 2 carcinomas , CIS; 1 papilloma, P) were retrospectively selected; immune infiltrate was assessed by histology and immunohistochemistry; RT-qPCR tested the expression of selected chemokines and EcPV-2 DNA and RNA. The results confirmed EcPV-2-L1 DNA in 18/20 (90%) samples. expression was instead retrieved in 13/20 cases (65%). The samples showed an increased infiltration of CD3lymphocytes, macrophages (MAC387; IBA1), plasma cells (MUM1), and FoxP3lymphocytes in the intra/peritumoral stroma when compared to extratumoral tissues ( < 0.05). Only MAC387neutrophils were increased in EcPV-2 viral load samples ( < 0.05). / was differentially expressed in EcPV and EcPV groups ( = 0.007). A significant decrease of and expression was highlighted in -positive samples ( < 0.05). IBA1 and CD20 were intratumorally increased in cases where IL-10 was expressed ( < 0.005). EpSCCs may represent a good spontaneous model for the human counterpart. Further prospective studies are needed in order to confirm these preliminary results.
Publication Date: 2020-10-27 PubMed ID: 33121116PubMed Central: PMC7693514DOI: 10.3390/cells9112364Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the immune environment within penile squamous cell carcinomas, a type of tumor common in older horses, as a model for similar cancers in humans. Their aim is to understand the role of certain chemokines and the EcPV-2 virus in these tumors.

Objectives and Methodology

  • The main objective of this study is to understand what goes on in the immune environment within equine penile squamous cell carcinomas, with the intent to use this knowledge to help treat the human variant of the disease.
  • A total of 20 equine penile epithelial tumors were selected for the study. Using techniques such as histology and immunohistochemistry, the researchers analyzed the infiltration of immune response cells, like lymphocytes and macrophages, within the tumors.
  • The researchers also used RT-qPCR, an advanced gene expression testing method, to find the presence and expression of EcPV-2 DNA and RNA, a papillomavirus considered the main cause of this type of cancer.

Findings

  • The study found the presence of EcPV-2-L1 DNA in 90% of the samples and RNA expression in 65% of the cases. This strengthens the link between the papillomavirus and this cancer.
  • They also observed an increased infiltration of various immune cells, like CD3 lymphocytes, macrophages, and plasma cells, in the intra and peritumoral stroma (tissue surrounding the tumor). This was in comparison to tissues that were not directly adjacent to the tumor.
  • Furthermore, there was increased presence of MAC387 neutrophils, a type of immune response cell, in samples with high EcPV-2 viral load.
  • The expression of certain chemokines, immune mediators, was found to be less in samples that were positive for EcPV-2.
  • Another finding was that the presence of IBA1 and CD20, markers linked to particular immune cells, was increased in cases where IL-10, an immune suppression molecule, was expressed.

Implications and Future Directions

  • The results from the study propose that equine squamous cell carcinomas could serve as a suitable model to study the human counterpart of the disease. This can help further our understanding and potentially lead to the development of targeted treatments.
  • Although this is a preliminary study, the results provide a foundation for future exploration in this area of research. The authors acknowledge the need for more investigations to confirm these results.

Cite This Article

APA
Porcellato I, Mecocci S, Mechelli L, Cappelli K, Brachelente C, Pepe M, Orlandi M, Gialletti R, Passeri B, Ferrari A, Modesto P, Ghelardi A, Razzuoli E. (2020). Equine Penile Squamous Cell Carcinomas as a Model for Human Disease: A Preliminary Investigation on Tumor Immune Microenvironment. Cells, 9(11), 2364. https://doi.org/10.3390/cells9112364

Publication

ISSN: 2073-4409
NlmUniqueID: 101600052
Country: Switzerland
Language: English
Volume: 9
Issue: 11
PII: 2364

Researcher Affiliations

Porcellato, Ilaria
  • Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
Mecocci, Samanta
  • Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
Mechelli, Luca
  • Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
Cappelli, Katia
  • Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
  • Centro di Ricerca sul Cavallo Sportivo, University of Perugia, 06126 Perugia, Italy.
Brachelente, Chiara
  • Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
Pepe, Marco
  • Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
  • Centro di Ricerca sul Cavallo Sportivo, University of Perugia, 06126 Perugia, Italy.
Orlandi, Margherita
  • Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
Gialletti, Rodolfo
  • Department of Veterinary Medicine, University of Perugia, 06126 Perugia, Italy.
  • Centro di Ricerca sul Cavallo Sportivo, University of Perugia, 06126 Perugia, Italy.
Passeri, Benedetta
  • Department of Veterinary Science, University of Parma, 43126 Parma, Italy.
Ferrari, Angelo
  • Zooprophylactic Institute of Piemonte, Liguria and Valle d'Aosta, 16129 Genova, Italy.
Modesto, Paola
  • Zooprophylactic Institute of Piemonte, Liguria and Valle d'Aosta, 16129 Genova, Italy.
Ghelardi, Alessandro
  • Azienda Usl Toscana Nord-Ovest, UOC Ostetricia e Ginecologia, Ospedale Apuane, 54100 Massa, Italy.
Razzuoli, Elisabetta
  • Zooprophylactic Institute of Piemonte, Liguria and Valle d'Aosta, 16129 Genova, Italy.

MeSH Terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / veterinary
  • Carcinoma, Squamous Cell / virology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Horses / immunology
  • Humans
  • Ki-67 Antigen / metabolism
  • Male
  • Papillomaviridae / physiology
  • Penile Neoplasms / immunology
  • Penile Neoplasms / pathology
  • Penile Neoplasms / veterinary
  • Penile Neoplasms / virology
  • Tumor Microenvironment / immunology
  • Viral Load
  • Viral Proteins / metabolism

Grant Funding

  • Grant 18C15 / funded by Italian Ministry of Health

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 58 references
  1. IARC CancerBases / Cancer Incidence in Five Continents, Vol. XI. [(accessed on 27 October 2020)]; Available online: https://publications.iarc.fr/Databases/Iarc-Cancerbases/Cancer-Incidence-In-Five-Continents-Vol.-XI-2017.
  2. Guan P, Howell-Jones R, Li N, Bruni L, de Sanjosé S, Franceschi S, Clifford GM. Human papillomavirus types in 115,789 HPV-positive women: a meta-analysis from cervical infection to cancer.. Int J Cancer 2012 Nov 15;131(10):2349-59.
    doi: 10.1002/ijc.27485pubmed: 22323075google scholar: lookup
  3. Canete-Portillo S, Sanchez DF, Cubilla AL. Pathology of Invasive and Intraepithelial Penile Neoplasia.. Eur Urol Focus 2019 Sep;5(5):713-717.
    doi: 10.1016/j.euf.2019.06.013pubmed: 31288989google scholar: lookup
  4. Alemany L, Cubilla A, Halec G, Kasamatsu E, Quirós B, Masferrer E, Tous S, Lloveras B, Hernández-Suarez G, Lonsdale R, Tinoco L, Alejo M, Alvarado-Cabrero I, Laco J, Guimerà N, Poblet E, Lombardi LE, Bergeron C, Clavero O, Shin HR, Ferrera A, Felix A, Germar J, Mandys V, Clavel C, Tzardi M, Pons LE, Wain V, Cruz E, Molina C, Mota JD, Jach R, Velasco J, Carrilho C, López-Revilla R, Goodman MT, Quint WG, Castellsagué X, Bravo I, Pawlita M, Muñoz N, Bosch FX, de Sanjosé S. Role of Human Papillomavirus in Penile Carcinomas Worldwide.. Eur Urol 2016 May;69(5):953-61.
    doi: 10.1016/j.eururo.2015.12.007pubmed: 26762611google scholar: lookup
  5. Iorga L, Dragos Marcu R, Cristina Diaconu C, Maria Alexandra Stanescu A, Pantea Stoian A, Liviu Dorel Mischianu D, Surcel M, Bungau S, Constantin T, Boda D, Fekete L, Gabriel Bratu O. Penile carcinoma and HPV infection (Review).. Exp Ther Med 2020 Jul;20(1):91-96.
    doi: 10.3892/etm.2019.8181pmc: PMC7273896pubmed: 32518604google scholar: lookup
  6. Djajadiningrat RS, Jordanova ES, Kroon BK, van Werkhoven E, de Jong J, Pronk DT, Snijders PJ, Horenblas S, Heideman DA. Human papillomavirus prevalence in invasive penile cancer and association with clinical outcome.. J Urol 2015 Feb;193(2):526-31.
    doi: 10.1016/j.juro.2014.08.087pubmed: 25150641google scholar: lookup
  7. Ottenhof SR, Djajadiningrat RS, Thygesen HH, Jakobs PJ, Jóźwiak K, Heeren AM, de Jong J, Sanders J, Horenblas S, Jordanova ES. The Prognostic Value of Immune Factors in the Tumor Microenvironment of Penile Squamous Cell Carcinoma.. Front Immunol 2018;9:1253.
    doi: 10.3389/fimmu.2018.01253pmc: PMC6004546pubmed: 29942303google scholar: lookup
  8. Doorbar J. Host control of human papillomavirus infection and disease.. Best Pract Res Clin Obstet Gynaecol 2018 Feb;47:27-41.
    doi: 10.1016/j.bpobgyn.2017.08.001pubmed: 28919159google scholar: lookup
  9. Béziat V. Human genetic dissection of papillomavirus-driven diseases: new insight into their pathogenesis.. Hum Genet 2020 Jun;139(6-7):919-939.
    doi: 10.1007/s00439-020-02183-xpmc: PMC7291412pubmed: 32435828google scholar: lookup
  10. Rector A, Van Ranst M. Animal papillomaviruses.. Virology 2013 Oct;445(1-2):213-23.
    doi: 10.1016/j.virol.2013.05.007pubmed: 23711385google scholar: lookup
  11. Munday JS, Thomson NA, Luff JA. Papillomaviruses in dogs and cats.. Vet J 2017 Jul;225:23-31.
    doi: 10.1016/j.tvjl.2017.04.018pubmed: 28720294google scholar: lookup
  12. Munday JS. Bovine and human papillomaviruses: a comparative review.. Vet Pathol 2014 Nov;51(6):1063-75.
    doi: 10.1177/0300985814537837pubmed: 24981715google scholar: lookup
  13. Sykora S, Brandt S. Papillomavirus infection and squamous cell carcinoma in horses.. Vet J 2017 May;223:48-54.
    doi: 10.1016/j.tvjl.2017.05.007pubmed: 28671071google scholar: lookup
  14. Lange CE, Zollinger S, Tobler K, Ackermann M, Favrot C. Clinically healthy skin of dogs is a potential reservoir for canine papillomaviruses.. J Clin Microbiol 2011 Feb;49(2):707-9.
    doi: 10.1128/JCM.02047-10pmc: PMC3043500pubmed: 21159938google scholar: lookup
  15. Doorbar J, Quint W, Banks L, Bravo IG, Stoler M, Broker TR, Stanley MA. The biology and life-cycle of human papillomaviruses.. Vaccine 2012 Nov 20;30 Suppl 5:F55-70.
    doi: 10.1016/j.vaccine.2012.06.083pubmed: 23199966google scholar: lookup
  16. Doorbar J, Egawa N, Griffin H, Kranjec C, Murakami I. Human papillomavirus molecular biology and disease association.. Rev Med Virol 2015 Mar;25 Suppl 1(Suppl Suppl 1):2-23.
    doi: 10.1002/rmv.1822pmc: PMC5024016pubmed: 25752814google scholar: lookup
  17. Ramsauer AS, Wachoski-Dark GL, Fraefel C, Tobler K, Brandt S, Knight CG, Favrot C, Grest P. Paving the way for more precise diagnosis of EcPV2-associated equine penile lesions.. BMC Vet Res 2019 Oct 22;15(1):356.
    doi: 10.1186/s12917-019-2097-0pmc: PMC6805557pubmed: 31640696google scholar: lookup
  18. Arthurs C, Suarez-Bonnet A, Willis C, Xie B, Machulla N, Mair TS, Cao K, Millar M, Thrasivoulou C, Priestnall SL, Ahmed A. Equine penile squamous cell carcinoma: expression of biomarker proteins and EcPV2.. Sci Rep 2020 May 12;10(1):7863.
    doi: 10.1038/s41598-020-64014-3pmc: PMC7217868pubmed: 32398763google scholar: lookup
  19. van den Top JG, de Heer N, Klein WR, Ensink JM. Penile and preputial squamous cell carcinoma in the horse: a retrospective study of treatment of 77 affected horses.. Equine Vet J 2008 Sep;40(6):533-7.
    doi: 10.2746/042516408X281171pubmed: 18487102google scholar: lookup
  20. Suárez-Bonnet A, Willis C, Pittaway R, Smith K, Mair T, Priestnall SL. Molecular carcinogenesis in equine penile cancer: A potential animal model for human penile cancer.. Urol Oncol 2018 Dec;36(12):532.e9-532.e18.
    doi: 10.1016/j.urolonc.2018.09.004pubmed: 30270026google scholar: lookup
  21. Smola S. Immunopathogenesis of HPV-Associated Cancers and Prospects for Immunotherapy.. Viruses 2017 Sep 12;9(9).
    doi: 10.3390/v9090254pmc: PMC5618020pubmed: 28895886google scholar: lookup
  22. Che Y, Yang Y, Suo J, An Y, Wang X. Induction of systemic immune responses and reversion of immunosuppression in the tumor microenvironment by a therapeutic vaccine for cervical cancer.. Cancer Immunol Immunother 2020 Dec;69(12):2651-2664.
    doi: 10.1007/s00262-020-02651-3pubmed: 32607768google scholar: lookup
  23. Chu C, Yao K, Lu J, Zhang Y, Chen K, Lu J, Zhang CZ, Cao Y. Immunophenotypes Based on the Tumor Immune Microenvironment Allow for Unsupervised Penile Cancer Patient Stratification.. Cancers (Basel) 2020 Jul 4;12(7).
    doi: 10.3390/cancers12071796pmc: PMC7407624pubmed: 32635549google scholar: lookup
  24. Vassallo J, Rodrigues AF, Campos AH, Rocha RM, da Cunha IW, Zequi SC, Guimarães GC, da Fonseca FP, Lopes A, Cubilla A, Soares FA. Pathologic and imunohistochemical characterization of tumoral inflammatory cell infiltrate in invasive penile squamous cell carcinomas: Fox-P3 expression is an independent predictor of recurrence.. Tumour Biol 2015 Apr;36(4):2509-16.
    doi: 10.1007/s13277-014-2864-2pubmed: 25557886google scholar: lookup
  25. Pérez J, Mozos E, Martín MP, Day MJ. Immunohistochemical study of the inflammatory infiltrate associated with equine squamous cell carcinoma.. J Comp Pathol 1999 Nov;121(4):385-97.
    doi: 10.1053/jcpa.1999.0336pubmed: 10542127google scholar: lookup
  26. Porcellato I, Modesto P, Cappelli K, Varello K, Peletto S, Brachelente C, Martini I, Mechelli L, Ferrari A, Ghelardi A, Razzuoli E. Equus caballus papillomavirus type 2 (EcPV2) in co-occurring vulvar and gastric lesions of a pony.. Res Vet Sci 2020 Oct;132:167-171.
    doi: 10.1016/j.rvsc.2020.06.003pubmed: 32590224google scholar: lookup
  27. Veyer D, Wack M, Grard O, Bonfils P, Hans S, Bélec L, Badoual C, Péré H. HPV detection and genotyping of head and neck cancer biopsies by molecular testing with regard to the new oropharyngeal squamous cell carcinoma classification based on HPV status.. Pathology 2019 Jun;51(4):421-425.
    doi: 10.1016/j.pathol.2019.02.002pubmed: 31005250google scholar: lookup
  28. Miglio A, Cappelli K, Capomaccio S, Mecocci S, Silvestrelli M, Antognoni MT. Metabolic and Biomolecular Changes Induced by Incremental Long-Term Training in Young Thoroughbred Racehorses during First Workout Season.. Animals (Basel) 2020 Feb 18;10(2).
    doi: 10.3390/ani10020317pmc: PMC7071023pubmed: 32085444google scholar: lookup
  29. Cappelli K, Felicetti M, Capomaccio S, Nocelli C, Silvestrelli M, Verini-Supplizi A. Effect of training status on immune defence related gene expression in Thoroughbred: are genes ready for the sprint?. Vet J 2013 Mar;195(3):373-6.
    doi: 10.1016/j.tvjl.2012.07.021pubmed: 22990119google scholar: lookup
  30. Crociati M, Capomaccio S, Mandara MT, Stradaioli G, Sylla L, Monaci M, Cappelli K. Different expression of Defensin-B gene in the endometrium of mares of different age during the breeding season.. BMC Vet Res 2019 Dec 21;15(1):465.
    doi: 10.1186/s12917-019-2215-zpmc: PMC6925900pubmed: 31864349google scholar: lookup
  31. Cappelli K, Amadori M, Mecocci S, Miglio A, Antognoni MT, Razzuoli E. Immune Response in Young Thoroughbred Racehorses under Training.. Animals (Basel) 2020 Oct 5;10(10).
    doi: 10.3390/ani10101809pmc: PMC7600081pubmed: 33027949google scholar: lookup
  32. Razzuoli E, Villa R, Ferrari A, Amadori M. A pig tonsil cell culture model for evaluating oral, low-dose IFN-α treatments.. Vet Immunol Immunopathol 2014 Aug 15;160(3-4):244-54.
    doi: 10.1016/j.vetimm.2014.05.011pubmed: 24951265google scholar: lookup
  33. Bosch FX, Broker TR, Forman D, Moscicki AB, Gillison ML, Doorbar J, Stern PL, Stanley M, Arbyn M, Poljak M, Cuzick J, Castle PE, Schiller JT, Markowitz LE, Fisher WA, Canfell K, Denny LA, Franco EL, Steben M, Kane MA, Schiffman M, Meijer CJ, Sankaranarayanan R, Castellsagué X, Kim JJ, Brotons M, Alemany L, Albero G, Diaz M, de Sanjosé S. Comprehensive control of human papillomavirus infections and related diseases.. Vaccine 2013 Dec 31;31 Suppl 7(Suppl 7):H1-31.
  34. Hibi H, Hatama S, Obata A, Shibahara T, Kadota K. Laryngeal squamous cell carcinoma and papilloma associated with Equus caballus papillomavirus 2 in a horse.. J Vet Med Sci 2019 Jul 19;81(7):1029-1033.
    doi: 10.1292/jvms.18-0461pmc: PMC6656819pubmed: 31167980google scholar: lookup
  35. Alloway E, Linder K, May S, Rose T, DeLay J, Bender S, Tucker A, Luff J. A Subset of Equine Gastric Squamous Cell Carcinomas Is Associated With Equus Caballus Papillomavirus-2 Infection.. Vet Pathol 2020 May;57(3):427-431.
    doi: 10.1177/0300985820908797pmc: PMC7335262pubmed: 32180540google scholar: lookup
  36. Muñoz N, Castellsagué X, Berrington de González A, Gissmann L. Chapter 1: HPV in the etiology of human cancer.. Vaccine 2006 Aug 31;24 Suppl 3:S3/1-10.
    doi: 10.1016/j.vaccine.2006.05.115pubmed: 16949995google scholar: lookup
  37. Lange CE, Tobler K, Lehner A, Grest P, Welle MM, Schwarzwald CC, Favrot C. EcPV2 DNA in equine papillomas and in situ and invasive squamous cell carcinomas supports papillomavirus etiology.. Vet Pathol 2013 Jul;50(4):686-92.
    doi: 10.1177/0300985812463403pubmed: 23064881google scholar: lookup
  38. Massa C, Seliger B. The tumor microenvironment: Thousand obstacles for effector T cells.. Cell Immunol 2019 Sep;343:103730.
    doi: 10.1016/j.cellimm.2017.12.004pubmed: 29249298google scholar: lookup
  39. van den Top JG, Harkema L, Lange C, Ensink JM, van de Lest CH, Barneveld A, van Weeren PR, Gröne A, Martens A. Expression of p53, Ki67, EcPV2- and EcPV3 DNA, and viral genes in relation to metastasis and outcome in equine penile and preputial squamous cell carcinoma.. Equine Vet J 2015 Mar;47(2):188-95.
    doi: 10.1111/evj.12245pubmed: 24898479google scholar: lookup
  40. Teh J, O'Connor E, O'Brien J, Lim WM, Taylor M, Heriot A, Ramsay R, Lawrentschuk N. Future directions in advanced penile cancer - mechanisms of carcinogenesis and a search for targeted therapy.. Future Oncol 2020 Oct;16(29):2357-2369.
    doi: 10.2217/fon-2020-0434pubmed: 32713198google scholar: lookup
  41. Wu S, Wu Y, Lu Y, Yue Y, Cui C, Yu M, Wang S, Liu M, Zhao Y, Sun Z. STAT1 expression and HPV16 viral load predict cervical lesion progression.. Oncol Lett 2020 Oct;20(4):28.
    doi: 10.3892/ol.2020.11889pmc: PMC7405543pubmed: 32774501google scholar: lookup
  42. Li CX, Chang WS, Mitsakos K, Rodger J, Holmes EC, Hudson BJ. Identification of a Novel Equine Papillomavirus in Semen from a Thoroughbred Stallion with a Penile Lesion.. Viruses 2019 Aug 4;11(8).
    doi: 10.3390/v11080713pmc: PMC6723834pubmed: 31382657google scholar: lookup
  43. Falini B, Fizzotti M, Pucciarini A, Bigerna B, Marafioti T, Gambacorta M, Pacini R, Alunni C, Natali-Tanci L, Ugolini B, Sebastiani C, Cattoretti G, Pileri S, Dalla-Favera R, Stein H. A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells, and activated T cells.. Blood 2000 Mar 15;95(6):2084-92.
    doi: 10.1182/blood.V95.6.2084pubmed: 10706878google scholar: lookup
  44. Lee HE, Luo L, Kroneman T, Passow MR, Del Rosario KM, Christensen MR, Francis ME, O'Shaughnessy JW, Blahnik AJ, Yang P, Yi ES. Increased Plasma Cells and Decreased B-cells in Tumor Infiltrating Lymphocytes are Associated with Worse Survival in Lung Adenocarcinomas.. J Clin Cell Immunol 2020;11(1).
    pmc: PMC7286600pubmed: 32523798
  45. Shalapour S, Font-Burgada J, Di Caro G, Zhong Z, Sanchez-Lopez E, Dhar D, Willimsky G, Ammirante M, Strasner A, Hansel DE, Jamieson C, Kane CJ, Klatte T, Birner P, Kenner L, Karin M. Immunosuppressive plasma cells impede T-cell-dependent immunogenic chemotherapy.. Nature 2015 May 7;521(7550):94-8.
    doi: 10.1038/nature14395pmc: PMC4501632pubmed: 25924065google scholar: lookup
  46. Wang L, Fu Y, Chu Y. Regulatory B Cells.. Adv Exp Med Biol 2020;1254:87-103.
    pubmed: 32323272doi: 10.1007/978-981-15-3532-1_8google scholar: lookup
  47. Attias M, Al-Aubodah T, Piccirillo CA. Mechanisms of human FoxP3(+) T(reg) cell development and function in health and disease.. Clin Exp Immunol 2019 Jul;197(1):36-51.
    doi: 10.1111/cei.13290pmc: PMC6591147pubmed: 30864147google scholar: lookup
  48. Shang B, Liu Y, Jiang SJ, Liu Y. Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis.. Sci Rep 2015 Oct 14;5:15179.
    doi: 10.1038/srep15179pmc: PMC4604472pubmed: 26462617google scholar: lookup
  49. Porcellato I, Brachelente C, De Paolis L, Menchetti L, Silvestri S, Sforna M, Vichi G, Iussich S, Mechelli L. FoxP3 and IDO in Canine Melanocytic Tumors.. Vet Pathol 2019 Mar;56(2):189-199.
    doi: 10.1177/0300985818808530pubmed: 30381008google scholar: lookup
  50. Sikora M, Kopeć B, Piotrowska K, Pawlik A. Role of allograft inflammatory factor-1 in pathogenesis of diseases.. Immunol Lett 2020 Feb;218:1-4.
    doi: 10.1016/j.imlet.2019.12.002pubmed: 31830499google scholar: lookup
  51. Legradi A, Dulka K, Jancsó G, Gulya K. Orofacial skin inflammation increases the number of macrophages in the maxillary subregion of the rat trigeminal ganglion in a corticosteroid-reversible manner.. Cell Tissue Res 2020 Dec;382(3):551-561.
    doi: 10.1007/s00441-020-03244-3pmc: PMC7683439pubmed: 32696216google scholar: lookup
  52. Karagianni AE, Lisowski ZM, Hume DA, Scott Pirie R. The equine mononuclear phagocyte system: The relevance of the horse as a model for understanding human innate immunity.. Equine Vet J 2021 Mar;53(2):231-249.
    doi: 10.1111/evj.13341pubmed: 32881079google scholar: lookup
  53. Lechien JR, Descamps G, Seminerio I, Furgiuele S, Dequanter D, Mouawad F, Badoual C, Journe F, Saussez S. HPV Involvement in the Tumor Microenvironment and Immune Treatment in Head and Neck Squamous Cell Carcinomas.. Cancers (Basel) 2020 Apr 25;12(5).
    doi: 10.3390/cancers12051060pmc: PMC7281394pubmed: 32344813google scholar: lookup
  54. Cai X, Zhang L, Wei W. Regulatory B cells in inflammatory diseases and tumor.. Int Immunopharmacol 2019 Feb;67:281-286.
    doi: 10.1016/j.intimp.2018.12.007pubmed: 30572252google scholar: lookup
  55. Xu M, Mizoguchi I, Morishima N, Chiba Y, Mizuguchi J, Yoshimoto T. Regulation of antitumor immune responses by the IL-12 family cytokines, IL-12, IL-23, and IL-27.. Clin Dev Immunol 2010;2010.
    pmc: PMC2946577pubmed: 20885915doi: 10.1155/2010/832454google scholar: lookup
  56. Zijlmans HJ, Punt S, Fleuren GJ, Trimbos JB, Kenter GG, Gorter A. Role of IL-12p40 in cervical carcinoma.. Br J Cancer 2012 Dec 4;107(12):1956-62.
    doi: 10.1038/bjc.2012.488pmc: PMC3516683pubmed: 23099807google scholar: lookup
  57. Gosmann C, Mattarollo SR, Bridge JA, Frazer IH, Blumenthal A. IL-17 suppresses immune effector functions in human papillomavirus-associated epithelial hyperplasia.. J Immunol 2014 Sep 1;193(5):2248-57.
    doi: 10.4049/jimmunol.1400216pmc: PMC4135400pubmed: 25063870google scholar: lookup
  58. Lin W, Niu Z, Zhang H, Kong Y, Wang Z, Yang X, Yuan F. Imbalance of Th1/Th2 and Th17/Treg during the development of uterine cervical cancer.. Int J Clin Exp Pathol 2019;12(9):3604-3612.
    pmc: PMC6949808pubmed: 31934210

Citations

This article has been cited 6 times.
  1. Cappelli K, Ciucis CG, Mecocci S, Nervo T, Crescio MI, Pepe M, Gialletti R, Pietrucci D, Migone LF, Turco S, Mechelli L, Passamonti F, Drago C, Donato GG, Varello K, Modesto P, Chillemi G, Ghelardi A, Razzuoli E. Detection of Equus Caballus Papillomavirus Type-2 in Asymptomatic Italian Horses. Viruses 2022 Jul 31;14(8).
    doi: 10.3390/v14081696pubmed: 36016317google scholar: lookup
  2. Mattei F, Alfaro C, Keisari Y. Cancer Immunology: From Molecular Mechanisms to Therapeutic Opportunities. Cells 2022 Jan 28;11(3).
    doi: 10.3390/cells11030459pubmed: 35159269google scholar: lookup
  3. Armando F, Mecocci S, Orlandi V, Porcellato I, Cappelli K, Mechelli L, Brachelente C, Pepe M, Gialletti R, Ghelardi A, Passeri B, Razzuoli E. Investigation of the Epithelial to Mesenchymal Transition (EMT) Process in Equine Papillomavirus-2 (EcPV-2)-Positive Penile Squamous Cell Carcinomas. Int J Mol Sci 2021 Sep 30;22(19).
    doi: 10.3390/ijms221910588pubmed: 34638929google scholar: lookup
  4. Porcellato I, Mecocci S, Brachelente C, Cappelli K, Armando F, Tognoloni A, Chiaradia E, Stefanetti V, Mechelli L, Pepe M, Gialletti R, Passeri B, Ghelardi A, Razzuoli E. PD-L1/PD-1 and CTLA-4 Expression in Equine Penile Squamous Cell Carcinomas. Animals (Basel) 2021 Jul 16;11(7).
    doi: 10.3390/ani11072121pubmed: 34359249google scholar: lookup
  5. Mecocci S, Porcellato I, Armando F, Mechelli L, Brachelente C, Pepe M, Gialletti R, Passeri B, Modesto P, Ghelardi A, Cappelli K, Razzuoli E. Equine Genital Squamous Cell Carcinoma Associated with EcPV2 Infection: RANKL Pathway Correlated to Inflammation and Wnt Signaling Activation. Biology (Basel) 2021 Mar 21;10(3).
    doi: 10.3390/biology10030244pubmed: 33801021google scholar: lookup
  6. Armando F, Godizzi F, Razzuoli E, Leonardi F, Angelone M, Corradi A, Meloni D, Ferrari L, Passeri B. Epithelial to Mesenchymal Transition (EMT) in a Laryngeal Squamous Cell Carcinoma of a Horse: Future Perspectives. Animals (Basel) 2020 Dec 7;10(12).
    doi: 10.3390/ani10122318pubmed: 33297475google scholar: lookup