Displaying the association between habits and PD-L1 expression. PD-L1: programmed death-ligand 1.
Declarations
Author contributions
NK: Conceptualization, Data curation, Writing—original draft, Writing—review & editing. KR: Conceptualization, Writing—original draft, Writing—review & editing, Supervision. PR: Conceptualization, Validation, Writing—review & editing, Supervision. MMM: Writing—original draft, Writing—review & editing. RF: Writing—original draft. DR: Visualization. MC and GM: Conceptualization, Validation, Writing—review & editing, Supervision. All authors read and approved the final manuscript.
Conflicts of interest
The authors declare that they have no conflicts of interest.
Ethical approval
Not applicable.
Consent to participate
Not applicable.
Consent to publication
Not applicable.
Availability of data and materials
The primary data for this systematic review were sourced online from databases listed in the methods. Reference articles are accessible on PubMed, Scopus, Web of Science, and Embase. Additional supporting data are available from the corresponding author upon request.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.
References
Chamoli A, Gosavi AS, Shirwadkar UP, Wangdale KV, Behera SK, Kurrey NK, et al. Overview of oral cavity squamous cell carcinoma: Risk factors, mechanisms, and diagnostics.Oral Oncol. 2021;121:105451. [DOI] [PubMed]
Solomon B, Young RJ, Rischin D. Head and neck squamous cell carcinoma: Genomics and emerging biomarkers for immunomodulatory cancer treatments.Semin Cancer Biol. 2018;52:228–40. [DOI] [PubMed]
Muthusamy M, Ramani P, Krishnan RP, K H, Sukumaran G, Ramasubramanian A. Oral Microflora and Its Potential Carcinogenic Effect on Oral Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.Cureus. 2023;15:e33560. [DOI] [PubMed] [PMC]
Surendran S, Krishnan RP, Ramani P, Ramalingam K, Jayaraman S. Role of Ceramide Synthase 1 in Oral Leukoplakia and Oral Squamous Cell Carcinoma: A Potential Linchpin for Tumorigenesis.Cureus. 2023;15:e42308. [DOI] [PubMed] [PMC]
Gintoni I, Vassiliou S, Chrousos GP, Yapijakis C. Review of Disease-Specific microRNAs by Strategically Bridging Genetics and Epigenetics in Oral Squamous Cell Carcinoma.Genes (Basel). 2023;14:1578. [DOI] [PubMed] [PMC]
Y D, Ramani P, Yuwanati M, Ramalingam K, S G. MicroRNA Profiling in Circulating Exosomes in Oral Squamous Cell Carcinoma: A Systematic Review.Cureus. 2023;15:e43235. [DOI] [PubMed] [PMC]
Starzyńska A, Sejda A, Adamski Ł, Adamska P, Pęksa R, Sakowicz-Burkiewicz M, et al. The B7 family molecules in oral squamous cell carcinoma: a systematic review. Part I: B7-H1 (PD-L1) and B7-DC (PD-L2).Postepy Dermatol Alergol. 2022;39:265–74. [DOI] [PubMed] [PMC]
Beyaert S, Borys A, Baldin P, Dahou H, Magremanne M, Mahy P, et al. Study of the PD-L1 expression, T-cells density and immunoscore in paired baseline tumor biopsies and surgical specimens in squamous cell carcinoma of the oral cavity.Oral Oncol. 2024;154:106869. [DOI] [PubMed]
Sasabe E, Tomomura A, Yamamoto T. The involvement of epidermal growth factor receptor/protein kinase B signaling in the tumor intrinsic PD-L1-induced malignant potential of oral squamous cell carcinoma.J Oral Pathol Med. 2024;53:310–20. [DOI] [PubMed]
Park R, Li J, Slebos RJC, Chaudhary R, Poole MI, Ferraris C, et al. Phase Ib trial of IRX-2 plus durvalumab in patients with recurrent and/or metastatic head and neck squamous cell carcinoma.Oral Oncol. 2024;154:106866. [DOI] [PubMed]
Kok VC. Current Understanding of the Mechanisms Underlying Immune Evasion From PD-1/PD-L1 Immune Checkpoint Blockade in Head and Neck Cancer.Front Oncol. 2020;10:268. [DOI] [PubMed] [PMC]
He J, Chen X, Xu M, Zhao J. Relationship of programmed death ligand-1 expression with clinicopathological features and prognosis in patients with oral squamous cell carcinoma: A meta-analysis.Arch Oral Biol. 2020;114:104717. [DOI] [PubMed]
Yang W, Wong MCM, Thomson PJ, Li K, Su Y. The prognostic role of PD-L1 expression for survival in head and neck squamous cell carcinoma: A systematic review and meta-analysis.Oral Oncol. 2018;86:81–90. [DOI] [PubMed]
Tang H, Zhou X, Ye Y, Zhou Y, Wu C, Xu Y. The different role of PD-L1 in head and neck squamous cell carcinomas: A meta-analysis.Pathol Res Pract. 2020;216:152768. [DOI] [PubMed]
Lenouvel D, González-Moles MÁ, Ruiz-Ávila I, Gonzalez-Ruiz L, Gonzalez-Ruiz I, Ramos-García P. Prognostic and clinicopathological significance of PD-L1 overexpression in oral squamous cell carcinoma: A systematic review and comprehensive meta-analysis.Oral Oncology. 2020;106:104722. [DOI] [PubMed]
Patel JJ, Levy DA, Nguyen SA, Knochelmann HM, Day TA. Impact of PD-L1 expression and human papillomavirus status in anti-PD1/PDL1 immunotherapy for head and neck squamous cell carcinoma-Systematic review and meta-analysis.Head Neck. 2020;42:774–86. [DOI] [PubMed] [PMC]
Troiano G, Caponio VCA, Zhurakivska K, Arena C, Pannone G, Mascitti M, et al. High PD-L1 expression in the tumour cells did not correlate with poor prognosis of patients suffering for oral squamous cells carcinoma: A meta-analysis of the literature.Cell Prolif. 2019;52:e12537. [DOI] [PubMed] [PMC]
Cheng L, Chai C, Liu Y, Jiao J. First‑line programmed cell death 1 inhibitor plus chemotherapy vs. standard treatment in patients with recurrent or metastatic oral squamous cell carcinoma: A retrospective cohort study.Oncol Lett. 2024;28:352. [DOI] [PubMed] [PMC]
Hayashi H, Nakagawa K. Combination therapy with PD-1 or PD-L1 inhibitors for cancer.Int J Clin Oncol. 2020;25:818–30. [DOI] [PubMed]
Ortona E, Pierdominici M, Rider V. Editorial: Sex Hormones and Gender Differences in Immune Responses.Front Immunol. 2019;10:1076. [DOI] [PubMed] [PMC]
Polanczyk MJ, Hopke C, Vandenbark AA, Offner H. Estrogen-mediated immunomodulation involves reduced activation of effector T cells, potentiation of Treg cells, and enhanced expression of the PD-1 costimulatory pathway.J Neurosci Res. 2006;84:370–8. [DOI] [PubMed]
Foy JP, Bertolus C, Michallet MC, Deneuve S, Incitti R, Bendriss-Vermare N, et al. The immune microenvironment of HPV-negative oral squamous cell carcinoma from never-smokers and never-drinkers patients suggests higher clinical benefit of IDO1 and PD1/PD-L1 blockade.Ann Oncol. 2017;28:1934–41. [DOI] [PubMed]
Lu H, Kuang D, Zhou P, Zeng J, Xia Q, Wang J, et al. PD-L1 expression in recurrent or metastatic head and neck squamous cell carcinoma in China (EXCEED study): a multicentre retrospective study.J Clin Pathol. 2025;78:88–95. [DOI] [PubMed] [PMC]
Xu J, editor. Regulation of Cancer Immune Checkpoints: Molecular and Cellular Mechanisms and Therapy. Springer Singapore; 2020. [DOI]
Tsushima F, Tanaka K, Otsuki N, Youngnak P, Iwai H, Omura K, et al. Predominant expression of B7-H1 and its immunoregulatory roles in oral squamous cell carcinoma.Oral Oncol. 2006;42:268–74. [DOI] [PubMed]
Dong Y, Wang Z, Mao F, Cai L, Dan H, Jiang L, et al. PD-1 blockade prevents the progression of oral carcinogenesis.Carcinogenesis. 2021;42:891–902. [DOI] [PubMed]
Ma S, Liu J, Jia R, Deng W, Jia J. Identification of a Favorable Prognostic Subgroup in Oral Squamous Cell Carcinoma: Characterization of ITGB4/PD-L1high with CD8/PD-1high.Biomolecules. 2023;13:1014. [DOI] [PubMed] [PMC]
Panarese I, Aquino G, Ronchi A, Longo F, Montella M, Cozzolino I, et al. Oral and Oropharyngeal squamous cell carcinoma: prognostic and predictive parameters in the etiopathogenetic route.Expert Rev Anticancer Ther. 2019;19:105–19. [DOI] [PubMed]
Kogashiwa Y, Yasuda M, Sakurai H, Nakahira M, Sano Y, Gonda K, et al. PD-L1 Expression Confers Better Prognosis in Locally Advanced Oral Squamous Cell Carcinoma.Anticancer Res. 2017;37:1417–24. [DOI] [PubMed]
Kitichotkul K, Lertprasertsuke N, Kintarak S, Pongsiriwet S, Powcharoen W, Iamaroon A. Expression of PD-L1 is HPV/P16-independent in oral squamous cell carcinoma.Heliyon. 2022;8:e10667. [DOI] [PubMed] [PMC]
Kim HS, Lee JY, Lim SH, Park K, Sun JM, Ko YH, et al. Association Between PD-L1 and HPV Status and the Prognostic Value of PD-L1 in Oropharyngeal Squamous Cell Carcinoma.Cancer Res Treat. 2016;48:527–36. [DOI] [PubMed] [PMC]
Subramaniam N, Nambiar A, Dhar S, Thankappan K, Koyakutty M, Balasubramanian D, et al. Low PDL1 Expression in Tumour Infiltrating Lymphocytes Predicts Local Recurrence in Oral Squamous Cell Carcinoma.Indian J Surg Oncol. 2021;12:408–14. [DOI] [PubMed] [PMC]
Pakkanen P, Ilmarinen T, Halme E, Irjala H, Koivunen P, Pukkila M, et al. Programmed death-ligand 1 and tumor-infiltrating lymphocytes (TILs) - low TIL density may predict poorer long-term prognosis in T1 laryngeal cancer.Virchows Arch. 2024;485:315–22. [DOI] [PubMed] [PMC]
Soopanit T, Laokulrath N, Chayopasakul V, Pongsapich W. Prognostic value and clinicopathological status of PD-L1 expression and CD8+ TILs in oral squamous cell cancer patients with or without traditional risk factors.Head Neck. 2023;45:1017–25. [DOI] [PubMed]
Cho YA, Yoon HJ, Lee JI, Hong S, Hong SD. Relationship between the expressions of PD-L1 and tumor-infiltrating lymphocytes in oral squamous cell carcinoma.Oral Oncol. 2011;47:1148–53. [DOI] [PubMed]
Bhardwaj M, Chiu MN, Pilkhwal Sah S. Adverse cutaneous toxicities by PD-1/PD-L1 immune checkpoint inhibitors: pathogenesis, treatment, and surveillance.Cutan Ocul Toxicol. 2022;41:73–90. [DOI] [PubMed]
Marabelle A, Fakih M, Lopez J, Shah M, Shapira-Frommer R, Nakagawa K, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study.Lancet Oncol. 2020;21:1353–65. [DOI] [PubMed]
Tang Q, Chen Y, Li X, Long S, Shi Y, Yu Y, et al. The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers.Front Immunol. 2022;13:964442. [DOI] [PubMed] [PMC]
Ai L, Xu A, Xu J. Roles of PD-1/PD-L1 Pathway: Signaling, Cancer, and Beyond.Adv Exp Med Biol. 2020;1248:33–59. [DOI] [PubMed]
Yu Y, Ni Z, Xu Y, Zhang L, Liu Y, Zeng F, et al. Multi-Functional AIE Phototheranostic Agent Enhancing αPD-L1 Response for Oral Squamous Cell Carcinoma Immunotherapy.Small. 2024;20:e2405470. [DOI] [PubMed]
Zou Y, Zhang H, Liu F, Chen Z, Tang H. Intratumoral microbiota in orchestrating cancer immunotherapy response.J Transl Int Med. 2025;12:540–2. [DOI] [PubMed] [PMC]
