Abstract
In oral squamous cell carcinoma (OSCC), expression of PDL1 is controversial with expressions showing a positive and negative correlation with survival in previous studies. Additionally, it is unclear whether expression on the tumour or tumour infiltrating lymphocytes (TIL) is a better predictor of survival. We performed this study on a cohort of Indian patients with OSCC to determine impact of PDL1 expression on survival. Retrospective analysis of 64 patients of OSCC treated with curative intent surgery with or without adjuvant therapy was performed. Stored tissue blocks were extracted and quantitative immunohistochemistry was performed for PDL1 expression separately on the tumour and the TIL using commercially available Dako kits. Correlation of clinical and pathological variables with PDL1 expression was performed using chi-square test. Survival analysis was performed using Kaplan-Meier method and Cox proportional hazards ratio. In our cohort, PDL1 expression was low, both in tumour (92% had <1% expression) and TIL (56% had <1% expression). Tumour low PDL1 expression (<1%) was associated with a higher risk of lymphovascular invasion (p = 0.044) and bone invasion (p = 0.01) but did not impact survival. Low TIL PDL1 expression (<1%) was more common in younger patients (<45 years) (p = 0.023) significantly predicting local recurrence (p = 0.02). PDL1 expression in OSCC was low. Low TIL PDL1 was common in younger patients and predicted local recurrence. Further study is required to better understand the relationship between age, tumour microenvironment and local recurrence.
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Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics,2012. CA Cancer J Clin 65:87–108
Asthana S, Patil RS, Labani S (2016) Tobacco-related cancers in India: a review of incidence reported from population-based cancer registries. Indian J Med Paediatr Oncol 37:152–157
Shingaki S, Takada M, Sasai K, Bibi R, Kobayashi T, Nomura T, Saito C (2003) Impact of lymph node metastasis on the pattern of failure and survival in oral carcinomas. Am J Surg 185:278–284
Azuma T, Yao S, Zhu G, Flies AS, Flies SJ, Chen L (2008) B7-H1 is a ubiquitous antiapoptotic receptor on cancer cells. Blood. 111:3635–3643
Sieviläinen M, Almahmoudi R, Al-Samadi A, Salo T, Pirinen M, Almangush A (2019) The prognostic value of immune checkpoints in oral squamous cell carcinoma. Oral Dis 25(6):1435–1445
Kim HR, Ha S-J, Hong MH, Heo SJ, Koh YW, Choi EC, Kim EK, Pyo KH, Jung I, Seo D, Choi J, Cho BC, Yoon SO (2016) PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients. Sci Rep 6:36956
Birtalan E, Danos K, Gurbi B, Brauswetter D, Halasz J, Piurko VK et al (2018) Expression of PD-L1 on immune cells shows better prognosis in laryngeal, oropharygeal, and hypopharyngeal cancer. Appl Immunohistochem Mol Morphol 26:e79–e85
Ruangritchankul K, Sandison A, Warburton F, Guerrero-Urbano T, Reis Ferreira M, Lei M, Thavaraj S (2019) Clinical evaluation of tumour-infiltrating lymphocytes as a prognostic factor in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma. Histopathology. 75:146–150
Subramaniam N, Balasubramanian D, Low TH, Vidhyadharan S, Menon A, Murthy S, Thankappan K, Clark JR, Gao K, Iyer S (2020) Squamous cell carcinoma of the oral tongue in young patients: outcomes and implications for treatment. Indian J Surg Oncol 22:1–7
Subramaniam N, Balasubramanian D, Murthy S, Vidhyadharan S, Thankappan K, Iyer S (2018) Oral cancer in the young with no tobacco exposure: a distinct epidemiological subset? J Head Neck Phys Surg 6(2):86–92
Chen XJ, Tan YQ, Zhang N, He MJ, Zhou G (2019) Expression of programmed cell death-ligand 1 in oral squamous cell carcinoma and oral leukoplakia is associated with disease progress and CD8+ tumor-infiltrating lymphocytes. Pathol Res Pract 215(6):152418
Cho YA, Yoon HJ, Lee JI, Hong SP, Hong SD (2011) Relationship between the expressions of PD-L1 and tumor-infiltrating lymphocytes in oral squamous cell carcinoma. Oral Oncol 47(12):1148–1153
Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F (2016) Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 375(19):1856–1867
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 squamous cell carcinoma. PLoS One 10(11):e0142656
de Vicente JC, Rodríguez-Santamarta T, Rodrigo JP, Blanco-Lorenzo V, Allonca E, García-Pedrero JM (2019) PD-L1 expression in tumor cells is an independent unfavorable prognostic factor in oral squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 28(3):546–554
Kaczmar J, Kompelli A, Graboyes E, Hornig J, Lentsch E, Day T, Paulos C, Young MR, Neskey D (2018) Phase 2 trial of nivolumab, an anti-PD-1 monoclonal antibody, as a novel neoadjuvant pre-surgical therapy for locally advanced oral cavity cancer. Int J Radiat Oncol Biol Phys 100(5):1315
Schoenfeld JD, Hanna GJ, Jo V, Criscitiello S, Rawal B, Catalano PS, Chau N, Lorch J, Kass J, Annino D, Goguen L (2020) Neoadjuvant Nivolumab+/-Ipilimumab in Patients with Oral Cavity Cancer. Int J Radiat Oncol Biol Phys 106(5):1114
Kowanetz M, Zou W, Gettinger SN, Koeppen H, Kockx M, Schmid P, Kadel EE III, Wistuba I, Chaft J, Rizvi NA, Spigel DR, Spira A, Hirsch FR, Cohen V, Smith D, Boyd Z, Miley N, Flynn S, Leveque V, Shames DS, Ballinger M, Mocci S, Shankar G, Funke R, Hampton G, Sandler A, Amler L, Mellman I, Chen DS, Hegde PS (2018) Differential regulation of PD-L1 expression by immune and tumor cells in NSCLC and the response to treatment with atezolizumab (anti-PD-L1). Proc Natl Acad Sci U S A 115:E10119–E10126
Troeltzsch M, Woodlock T, Pianka A, Otto S, Troeltzsch M, Ehrenfeld M, Knösel T (2017) Is there evidence for the presence and relevance of the PD-1/PD-L1 pathway in oral squamous cell carcinoma? Hints from an immunohistochemical study. J Oral Maxillofac Surg 75(5):969–977
Siegelmann-Danieli N, Hanlon A, Ridge JA, Padmore R, Fein DA, Langer CJ (1998) Oral tongue cancer in patients less than 45 years old: institutional experience and comparison with older patients. J Clin Oncol 16:745–753
Kuriakose M, Sankaranarayanan M, Nair MK, Cherian T, Sugar AW, Scully C, Prime SS (1992) Comparison of oral squamous cell carcinoma in younger and older patients in India. Eur J Cancer B Oral Oncol 28:113–120
Veness MJ, Morgan GJ, Sathiyaseelan Y, Gebski V (2005) Anterior tongue cancer and the incidence of cervical lymph node metastases with increasing tumour thickness: should elective treatment to the neck be standard practice in all patients? ANZ J Surg 75:101–105
Ho HC, Lee MS, Hsiao SH, Hwang JH, Hung SK, Chou P, Lee CC (2008) Squamous cell carcinoma of the oral cavity in young patients: a matched-pair analysis. Eur Arch Otorhinolaryngol 265(1):57–61
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Institution where work was done: Amrita Institute of Medical Sciences, Kochi, Kerala, India and Mazumdar Shaw Medical Foundation, Bangalore, India
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Subramaniam, N., Nambiar, A., Dhar, S. et al. Low PDL1 Expression in Tumour Infiltrating Lymphocytes Predicts Local Recurrence in Oral Squamous Cell Carcinoma. Indian J Surg Oncol 12, 408–414 (2021). https://doi.org/10.1007/s13193-021-01333-5
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DOI: https://doi.org/10.1007/s13193-021-01333-5