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01-04-2019 | Original Article

Reduced CD8⁺ T cells infiltration can be associated to a malignant transformation in potentially malignant oral epithelial lesions

Authors: Aline Lauda Freitas Chaves, Ana Gabriela Silva, Flávia Medeiros Maia, Gabriela Francine Martins Lopes, Luiz Fernando Barbosa de Paulo, Luciana Vieira Muniz, Hélio Batista dos Santos, João Marcos Arantes Soares, Alexandre Andrade Souza, Leandro Augusto de Oliveira Barbosa, Adriano Mota Loyola, Eddie Fernando Candido Murta, Márcia Antoniaze Michelin, Rosy Iara Maciel de Azambuja Ribeiro

Published in: Clinical Oral Investigations | Issue 4/2019

Abstract

Objective

The aim of this study was to evaluate the immunohistochemical expressions of PD1, CD4⁺, and CD8⁺ in premalignant lesions (OPML) that were transformed into oral squamous cell carcinoma OSCC (OPML-OSCC), in OSCC and also in premalignant lesions that were not transformed into OSCC (OPML-NOSSC).

Materials and methods

Retrospective analyses were performed in order to verify the demographic characteristics of the patients. CD4, CD8, and PD1 IMH studies were carried out on OPML and OSCC samples from 11 patients with OPML-OSCC and OPML, together with samples from 14 patients with OPML-NOSCC. The differences between OPML-OSCC and OPML-NOSCC were analyzed.

Results

Non-homogenous leukoplakia, together with the related oral subsite, and the lack of an exposure to tobacco, were all associated with malignant transformations. There were no statistical differences in the PD1 expression and the CD4⁺ cells in OPML-OSCC and OPML-NOSCC. A significant increment in the CD8⁺ cells was noted in the OPML that evolved into carcinomas when compared with OPML-NOSCC (p = 0.05), whereas there were higher CD8⁺ cells levels in the carcinomas when compared with the OPML that evolved into carcinomas (p = 0.027).

Conclusions

CD8⁺ cells infiltrate more in OPML-NOSCC than in OPML-OSCC. Carcinoma is more infiltrated by CD8⁺ cells than its associated OPML.

Clinical relevance

Understanding immunological factors associated with malignant transformation of oral premalignant lesions can open a new way to treat this disease.

Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917. https://doi.org/10.1002/ijc.25516 CrossRefPubMed

Neville B, Damm D, Allen C, Bouquot J (2009) Oral and maxillofacial pathology. Saunders/Elsevier, St. Louis

Warnakulasuriya S1, Johnson NW, van der Waal I (2007 Nov) Nomenclature and classification of potentially malignant disorders of the oral mucosa. J Oral Pathol Med 36(10):575–580. https://doi.org/10.1111/j.1600-0714.2007.00582.x CrossRefPubMed

Napier SS, Speight PM (2008) Natural history of potentially malignant oral lesions and conditions: an overview of the literature. J Oral Pathol Med 37:1–10. https://doi.org/10.1111/j.1600-0714.2007.00579.x CrossRefPubMed

Wojtowicz ME, Dunn BK, Umar A (2016) Immunologic approaches to cancer prevention-current status, challenges, and future perspectives. Semin Oncol 43:161–172. https://doi.org/10.1053/j.seminoncol.2015.11.001 CrossRefPubMed

Willian WNJ (2012) Oral premalignant lesions: any progress with systemic therapies? Curr Opin Oncol 24:205–210. https://doi.org/10.1097/CCO.0b013e32835091bd CrossRef

Quan H, Fang L, Pan H, Deng Z, Gao S, Liu O, Wang Y, Hu Y, Fang X, Yao Z, Guo F, Lu R, Xia K, Tang Z (2016) An adaptive immune response driven by mature, antigen-experienced T and B cells within the microenvironment of oral squamous cell carcinoma. Int J Cancer 138:2952–2962. https://doi.org/10.1002/ijc.30019 CrossRefPubMed

Kaur J, Jacobs R (2015 Aug) Proinflammatory cytokine levels in oral lichen planus, oral leukoplakia, and oral submucous fibrosis. J Korean Assoc Oral Maxillofac Surg 41(4):171–175. https://doi.org/10.5125/jkaoms.2015.41.4.171 CrossRefPubMedPubMedCentral

Mori K, Haraguchi S, Hiori M, Shimada J, Ohmori Y (2015) Tumor-associated macrophages in oral premalignant lesions coexpress CD163 and STAT1 in a Th1-dominated microenvironment. BMC Cancer 15:573. https://doi.org/10.1186/s12885-015-1587-0 CrossRefPubMedPubMedCentral

10.

Lee JJ, Lin CL, Chen TH, Kok SH, Chang MC, Jeng JH. Changes in peripheral blood lymphocyte phenotypes distribution in patients with oral cancer/oral leukoplakia in Taiwan Int J Oral Maxillofac Surg 2010 39(8):806-814. doi: https://doi.org/10.1016/j.ijom.2010.04.045.

11.

Fan CC, Wang TY, Cheng YA, Jiang SS, Cheng CW, Lee AY, Kao TY (2013) Expression of E-cadherin, twist and p53 and their prognostic value in patients with oral squamous cell carcinoma. J Cancer Res Clin Oncol 139:1735–1744. https://doi.org/10.1007/s00432-013-1499-9 CrossRefPubMed

12.

Rhodus NL, Kerr RA, Patel K (2014) Leukoplakia, premalignancy and squamous cell carcinoma. Dent Clin N Am 58:315–340. https://doi.org/10.1016/j.cden.2013.12.004 CrossRefPubMed

13.

Anderson A, Ishak N (2015) Marked variation in malignant transformation rates of oral leukoplakia. Evid-Based Dent 16:102–103. https://doi.org/10.1038/sj.ebd.6401128 CrossRefPubMed

14.

Dietrich T, Reichart PA, Scheifele C (2004) Clinical risk factors of oral leukoplakia in a representative sample of the US population. Oral Oncol 40:158–163. https://doi.org/10.1016/S1368-8375(03)00145-3 CrossRefPubMed

15.

Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer statistics review, 1975-2013, National Cancer Institute

16.

Johnson SD, Levingston C, Young MRI (2016) Premalignant oral lesion cells elicit increased cytokine production and activation of T-cells. Anticancer Res 36:3261–3270PubMedPubMedCentral

17.

Woodford D, Johnson SD, Costa AM, Young MR (2014) An inflammatory cytokine milieu is prominent in premalignant oral lesions, but subsides when lesions progress to squamous cell carcinoma. J Clin Cell Immunol 5:1–17. https://doi.org/10.4172/2155-9899.1000230 CrossRef

18.

Badoual C, Hans S, Rodriguez J, Peyrard S, Klein C, Agueznay NEH, Mosseri V, Laccourreye O, Bruneval P, Fridman WH, Brasnu DF, Tartour E (2006) Prognostic value of tumour-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res 12:465–472. https://doi.org/10.1158/1078-0432.CCR-05-1886 CrossRefPubMed

19.

Öhman J, Mowjood R, Larsson L, Kovacs A, Magnusson B, Kjeller G, Jontell M, Hasseus B (2015) Presence of CD3-positive T-cells in oral premalignant leukoplakia indicates prevention of cancer transformation. Anticancer Res 35:311–318PubMed

20.

Piva MR, Souza LB, Martins-Filho PR, Soares RC, Santos TS, Andrade ESS (2011) Role of inflammation in oral carcinogenesis (part I): histological grading of malignancy using a binary system. Oncol Lett 2:1225–1231. https://doi.org/10.3892/ol.2011.382 CrossRefPubMedPubMedCentral

21.

Maleki S, Schlecht NF, Keller C, Diaz J, Moss J, Prystowsky MB, Macian F, Brandwein-Gensler M (2011) Lymphocytic host response to oral squamous cell carcinoma: an adaptive T-cell response at the tumour interface. Head Neck Pathol 5:117–122. https://doi.org/10.1007/s12105-011-0247-1 CrossRefPubMedPubMedCentral

22.

Gannot G, Gannot I, Vered H, Buchner A, Keisari Y (2002) Increase in immune cell infiltration with progression of oral epithelium from hyperkeratosis to dysplasia and carcinoma. Br J Cancer 86:1444–1448CrossRefPubMedPubMedCentral

23.

Aghbari SMH, Abushouk AI, Shakir OG, Zayed SO, Attia A. Correlation between tissue expression of microRNA-137 and CD8 in oral lichen planus.Clin Oral Investig [15 Oct 2017, 22(3):1463–1467]. DOI: https://doi.org/10.1007/s00784-017-2252-6

24.

Enomoto A, Sato E, Yasuda T, Isomura T, Nagao T, Chikazu D (2018 Apr) Intraepithelial CD8+ lymphocytes as a predictive diagnostic biomarker for the remission of oral lichen planus. Hum Pathol 74:43–53. https://doi.org/10.1016/j.humpath.2017.12.008 CrossRefPubMed

25.

Brahmbhatt B, Vora H, Shah B (2016) Infiltration of T cell subsets during oral carcinogenesis. Indian J Oral Sci 7:28–41CrossRef

26.

Cho YA, Yoon HJ, Lee JI, Hong SP, Hong SD (2011) Relationship between the expressions of PD-L1 and tumour-infiltrating lymphocytes in oral squamous cell carcinoma. Oral Oncol 47:1148–1153. https://doi.org/10.1016/j.oraloncology.2011.08.007 CrossRefPubMed

27.

Lin YM, Sung WW, Hsieh MJ, Tsai SC, Lai HW, Yang SM, Shen KH, Chen MK, Lee H, Yeh KT, Chen CJ (2015) High PD-L1 expression correlates with metastasis and poor prognosis in oral Ssquamous cell carcinoma. PLoS One 10:e0142656. https://doi.org/10.1371/journal.pone.0142656 CrossRefPubMedPubMedCentral

28.

Straub M, Drecoll E, Pfarr N, Weichert W, Langer R, Hapfelmeier A, Götz C, Wolff KD, Kolk A, Specht K (2016) CD274/PD-L1 gene amplification and PD-L1 protein expression are common events in squamous cell carcinoma of the oral cavity. Oncotarget 7: 12024–12034. Doi: https://doi.org/10.18632/oncotarget.7593

29.

Ryan BM, Faupel-Badger JM (2016) The hallmarks of premalignant conditions: a molecular basis for cancer prevention. Semin Oncol 43:22–35CrossRefPubMed

Title: Reduced CD8+ T cells infiltration can be associated to a malignant transformation in potentially malignant oral epithelial lesions
Authors: Aline Lauda Freitas Chaves
Ana Gabriela Silva
Flávia Medeiros Maia
Gabriela Francine Martins Lopes
Luiz Fernando Barbosa de Paulo
Luciana Vieira Muniz
Hélio Batista dos Santos
João Marcos Arantes Soares
Alexandre Andrade Souza
Leandro Augusto de Oliveira Barbosa
Adriano Mota Loyola
Eddie Fernando Candido Murta
Márcia Antoniaze Michelin
Rosy Iara Maciel de Azambuja Ribeiro
Publication date: 01-04-2019
Publisher: Springer Berlin Heidelberg
Published in: Clinical Oral Investigations / Issue 4/2019
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-018-2622-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Reduced CD8⁺ T cells infiltration can be associated to a malignant transformation in potentially malignant oral epithelial lesions

Abstract

Objective

Materials and methods

Results

Conclusions

Clinical relevance

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objective

Materials and methods

Results

Conclusions

Clinical relevance

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