ROLE OF CD8+ TUMOUR-INFILTRATING LYMPHOCYTES IN PREDICTING REGIONAL LYMPH NODE METASTASIS IN LIP AND ORAL CAVITY SQUAMOUS CELL CARCINOMA
DOI:
https://doi.org/10.55519/JAMC-02-11654Keywords:
CD8 antigen (CD8), CD8-positive T-lymphocytes, immunohistochemistry, lip, lymphatic metastasis, oral cavity, squamous cell carcinoma, tumor-infiltrating lymphocytes (T.I.L.s)Abstract
Background: Lip and oral squamous cell carcinoma maintains a significant disease burden in Pakistan. The latest research on cancer focuses more on the role of body’s immune response in tumour progression and spread rather than on the nature of neoplastic cells. Tumour-infiltrating lymphocytes constitute a major part of tumour microenvironment and infiltration of tumour stroma by cytotoxic T-cells are known to limit the tumour progression in various malignancies, such as, colorectal and stomach cancers. In our study, we aim to establish the prognostic role of CD8+ tumour-infiltrating lymphocytes in lip and oral squamous cell carcinoma. Methods: Clinico-pathological data and paraffin-embedded blocks were obtained for 100 cases of lip and oral squamous cell carcinoma. These cases were selected through non-probability, convenience sampling at the Histopathology department of A.F.I.P., Rawalpindi. Fresh sections from the tumour proper were taken and CD8 immuno-marker was applied. Data was recorded, entered and analyzed with S.P.S.S. version 27.0 and Microsoft Excel. Qualitative variables were represented as frequency/percentages and quantitative variables were represented as mean and standard deviation. Chi-squared test was applied to test association between categorical data. A p-value of <0.05 was taken as significant. Results: Increased CD8 T.I.L. density was significantly associated with pN stage (p-value= .000) and early clinical stage (p-value= .014). No significant association with other clinico-pathological parameters was established. Conclusion: CD8 T.I.L. density is a reliable marker for predicting absence or presence of cervical nodal metastasis in lip and oral S.C.C. Its predictive role in determining overall survival rate should be evaluated in future studies.References
Qureshi MA, Syed SA, Sharafat S. Lip and oral cavity cancers (C00-C06) from a mega city of Pakistan: Ten-year data from the Dow Cancer Registry. J Taibah Univ Med Sci 2021;16(4):624–7.
Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, et al. Global Cancer Observatory: Cancer Today [Internet]. Lyon, France: International Agency for Research on Cancer; 2021 [cited 2022 May 19]. Available from: https://gco.iarc.fr/today
Bai XX, Zhang J, Wei L. Analysis of primary oral and oropharyngeal squamous cell carcinoma in inhabitants of Beijing, China—a 10-year continuous single-center study. BMC Oral Health 2020;20(1):208.
Nocini R, Lippi G, Mattiuzzi C. Biological and epidemiologic updates on lip and oral cavity cancers. Ann Cancer Epidemiol 2020;4:1–6.
Chen S, Lin Z, Chen J, Yang A, Zhang Q, Xie C, et al. Older age is a risk factor associated with poor prognosis of patients with squamous cell carcinoma of the oral cavity. Eur Arch Otorhinolaryngol 2020;277(9):2573–80.
Madera M, Amador LT, Acosta CL. Therapeutic options in unresectable oral squamous cell carcinoma: A systematic review. Cancer Manag Res 2021;13:6705–19.
Bugshan A, Farooq I. Oral squamous cell carcinoma: metastasis, potentially associated malignant disorders, etiology and recent advancements in diagnosis. F1000Res 2020;9:229.
Wang M, Zhao J, Zhang L, Wei F, Lian Y, Wu Y, et al. Role of tumour microenvironment in tumourigenesis. J Cancer 2017;8(5):761–73.
Steele KE, Tan TH, Korn R, Dacosta K, Brown C, Kuziora M, et al. Measuring multiple parameters of CD8+ tumour-infiltrating lymphocytes in human cancers by image analysis. J Immunother Cancer 2018;6(1):20.
Idos GE, Kwok J, Bonthala N, Kysh L, Gruber SB, Qu C. The prognostic implications of tumour infiltrating lymphocytes in colorectal cancer: a systematic review and meta-analysis. Sci Rep 2020;10(1):3360.
Lee JS, Won HS, Hong JH, Ko YH. Prognostic role of tumour-infiltrating lymphocytes in gastric cancer: a systematic review and meta-analysis. Medicine (Baltimore) 2018;97(32):e11769.
Rashed HE, Abdelrahman AE, Abdelgawad M, Balata S, Shabrawy ME. Prognostic significance of programmed cell death ligand 1 (PD-L1), CD8+ tumour-infiltrating lymphocytes and p53 in non-small cell lung cancer: an immunohistochemical study. Turk Patoloji Derg 2017;1(1):211–22.
Fang J, Li X, Ma D, Liu X, Chen Y, Wang Y, et al. Prognostic significance of tumour infiltrating immune cells in oral squamous cell carcinoma. BMC Cancer 2017;17(1):375.
Książek M, Lewandowski B, Brodowski R, Pakla P, Kawalec-Książek M, Fudali L, et al. The prognostic significance of tumour infiltrating lymphocytes in oral squamous cell carcinoma. Pol J Pathol 2019;70(4):277–85.
Borsetto D, Tomasoni M, Payne K, Polesel J, Deganello A, Bossi P, et al. Prognostic significance of CD4+ and CD8+ tumour-infiltrating lymphocytes in head and neck squamous cell carcinoma: a meta-analysis. Cancers (Basel) 2021;13(4):781.
Shaban M, Khurram SA, Fraz MM, Alsubaie N, Masood I, Mushtaq S, et al. A novel digital score for abundance of tumour infiltrating lymphocytes predicts disease free survival in oral squamous cell carcinoma. Sci Rep 2019;9(1):13341.
Qi X, Jia B, Zhao X, Yu D. Advances in T-cell checkpoint immunotherapy for head and neck squamous cell carcinoma. OncoTargets Ther 2017;10:5745–54.
Badar F, Mahmood S. Hospital-based cancer profile at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, pakistan. J Coll Physicians Surg Pak 2015;25(4):259–63.
Nocini R, Lippi G, Mattiuzzi C. Biological and epidemiologic updates on lip and oral cavity cancers. Ann Cancer Epidemiol 2020;4(1):1–6.
Shield KD, Ferlay J, Jemal A, Sankaranarayanan R, Chaturvedi AK, Bray F, et al. The global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012. CA Cancer J Clin 2017;67(1):51–64.
OpenEpi.com [Internet]. OpenEpi: Open-Source Epidemiologic Statistics for Public Health, Version 3 [cited 2022 Dec 25]. Available from: https://www.openepi.com/SampleSize/SSPropor.htm
Rathore AS, Kumar S, Konwar R, Makker A, Negi MP, Goel MM. CD3+, CD4+ & CD8+ tumour infiltrating lymphocytes (TILs) are predictors of favourable survival outcome in infiltrating ductal carcinoma of breast. Indian J Med Res 2014;140(3):361–9.
Charly MM, Jean-PauI SI, Hippolyte SNT, Erick KN, Alifi PB, Adelin NF, et al. Review of the Literature on Oral Cancer: Epidemiology, Management and Evidence-based Traditional Medicine Treatment. Ann Res Rev Biol 2022;30:15–27.
Suresh GM, Koppad R , Prakash BV, Sabitha KS, Dhara PS. Prognostic Indicators of Oral Squamous Cell Carcinoma. Ann Maxillofac Surg 2019;9(2):364–70.
Haidari S, Obermeier KT, Kraus M, Otto S, Probst FA, Liokatis P. Nodal Disease and Survival in Oral Cancer: Is Occult Metastasis a Burden Factor Compared to Preoperatively Nodal Positive Neck? Cancers (Basel) 2022;14(17):4241.
Takada K, Kashiwagi S, Asano Y, Goto W, Kouhashi R, Yabumoto A, et al. Prediction of lymph node metastasis by tumour-infiltrating lymphocytes in T1 breast cancer. BMC Cancer 2020;20(1):598.
Sahaf R, Naseem N, Anjum R, Nagi AH, Path F. A study of 89 cases of oral squamous cell carcinoma presenting at Teaching Hospitals of Lahore, Pakistan. JPDA 2017;26(01):27–31.
Santos Pereira Jd, da Costa Miguel MC, Guedes Queiroz LM, da Silveira ÉJD. Analysis of CD8+ and CD4+ Cells in Oral Squamous Cell Carcinoma and Their Association With Lymph Node Metastasis and Histologic Grade of Malignancy. Appl Immunohistochem Mol Morphol 2014;22(3):200–205.
Shimizu S, Hiratsuka H, Koike K, Tsuchihashi K, Sonoda T, Ogi K, et al. Tumour-infiltrating CD8+ T-cell density is an independent prognostic marker for oral squamous cell carcinoma. Cancer Med 2019;8(1):80–93.
Caruntu A, Moraru L, Lupu M, Vasilescu F, Dumitrescu M, Cioplea M, et al. Prognostic Potential of Tumour-Infiltrating Immune Cells in Resectable Oral Squamous Cell Carcinoma. Cancers (Basel) 2021;13(9):2268.
Huang Z, Xie N, Liu H, Wan Y, Zhu Y, Zhang M, et al. The prognostic role of tumour-infiltrating lymphocytes in oral squamous cell carcinoma: A meta-analysis. J Oral Pathol Med 2019;48(9):788–98.
Espinosa E, Márquez-Rodas I, Soria A, Berrocal A, Manzano JL, Gonzalez-Cao M, et al. Martin-Algarra S, Spanish Melanoma Group. Predictive factors of response to immunotherapy—a review from the Spanish Melanoma Group (GEM). Ann Transl Med 2017;5(19):389.
Downloads
Published
Issue
Section
License
Copyright (c) 2023 Zainab Asif Sukhera, Nadeem Zafar, Nighat Ara, Saadia Muneer, Azka Haroon, Zunaira Saeed
This work is licensed under a Creative Commons Attribution-NoDerivatives 4.0 International License.
Journal of Ayub Medical College, Abbottabad is an OPEN ACCESS JOURNAL which means that all content is FREELY available without charge to all users whether registered with the journal or not. The work published by J Ayub Med Coll Abbottabad is licensed and distributed under the creative commons License CC BY ND Attribution-NoDerivs. Material printed in this journal is OPEN to access, and are FREE for use in academic and research work with proper citation. J Ayub Med Coll Abbottabad accepts only original material for publication with the understanding that except for abstracts, no part of the data has been published or will be submitted for publication elsewhere before appearing in J Ayub Med Coll Abbottabad. The Editorial Board of J Ayub Med Coll Abbottabad makes every effort to ensure the accuracy and authenticity of material printed in J Ayub Med Coll Abbottabad. However, conclusions and statements expressed are views of the authors and do not reflect the opinion/policy of J Ayub Med Coll Abbottabad or the Editorial Board.
USERS are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author. This is in accordance with the BOAI definition of open access.
AUTHORS retain the rights of free downloading/unlimited e-print of full text and sharing/disseminating the article without any restriction, by any means including twitter, scholarly collaboration networks such as ResearchGate, Academia.eu, and social media sites such as Twitter, LinkedIn, Google Scholar and any other professional or academic networking site.