Year 2025,
Volume: 42 Issue: 4, 411 - 416, 31.12.2025
Berkan Düzgün
,
Özgür Kemal
,
Yasemin Kemal
,
Seda Gün
,
Emre Demirel
References
-
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
-
Marur S, Forastiere AA. Head and neck cancer: changing epidemiology, diagnosis, and treatment. Mayo Clin Proc.
2008;83(4):489-501.
-
Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Platinum-based chemotherapy plus
cetuximab in head and neck cancer. N Engl J Med. 2008;359(11):1116-27.
-
Machiels JP, René Leemans C, Golusinski W, Grau C, Licitra L, Gregoire V. Squamous cell carcinoma of the oral
cavity, larynx, oropharynx and hypopharynx: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis,
treatment and follow-up. Ann Oncol. 2020;31(11):1462-75.
-
Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol.
2008;26:677-704.
-
Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell
apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793-800.
-
Qiao XW, Jiang J, Pang X, Huang MC, Tang YJ, Liang XH, et al. The Evolving Landscape of PD-1/PD-L1 Pathway in
Head and Neck Cancer. Front Immunol. 2020;11:1721.
-
Lenouvel D, González-Moles M, 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 Oncol. 2020;106:104722.
-
Mishra PS, Sidhu A, Dwivedi G, Mulajker DS, Awasthi S. Determining PD-L1 expression in head and neck squamous
cell carcinoma using immunohistochemistry. Indian J Cancer. 2022;59(4):474-9.
-
Ferris RL. Immunology and Immunotherapy of Head and Neck Cancer. J Clin Oncol. 2015;33(29):3293-304.
-
Sanchez-Canteli M, Granda-Díaz R, Del Rio-Ibisate N, Allonca E, López-Alvarez F, Agorreta J, et al. PD-L1 expression
correlates with tumor-infiltrating lymphocytes and better prognosis in patients with HPV-negative head and neck
squamous cell carcinomas. Cancer Immunol Immunother. 2020;69(10):2089-100.
-
Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G, Jr., et al. Pembrolizumab alone or with
chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the
head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):1915-28.
-
Ou D, Adam J, Garberis I, Blanchard P, Nguyen F, Levy A, et al. Clinical relevance of tumor infiltrating lymphocytes,
PD-L1 expression and correlation with HPV/p16 in head and neck cancer treated with bio- or chemo-radiotherapy.
Oncoimmunology. 2017;6(9):e1341030.
-
Lenouvel D, González-Moles M, Ruiz-Ávila I, Chamorro-Santos C, González-Ruiz L, González-Ruiz I, et al.
Clinicopathological and prognostic significance of PD-L1 in oral cancer: A preliminary retrospective
immunohistochemistry study. Oral Dis. 2021;27(2):173-82.
-
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(1):152768.
-
Malik IS, Asif M, Bashir N, Ara N, Rashid F, Din HU, et al. Frequency of Expression of PD-1 andPD-L1 in Head and Neck
Squamous Cell Carcinoma and Their Association With Nodal Metastasis: A Cross-Sectional Study. Asian Pacific
Journal of Cancer Prevention. 2022;23(2):467-73.
-
Moratin J, Metzger K, Safaltin A, Herpel E, Hoffmann J, Freier K, et al. Upregulation of PD‐L1 and PD‐L2 in Neck Node
Metastases of Head and Neck Squamous Cell Carcinoma. Head & Neck. 2019;41(8):2484-91.
-
Kamiya S, Kato J, Kamiya T, Yamashita T, Sumikawa Y, Hida T, et al. Association Between PD‐L1 Expression and
Lymph Node Metastasis in Cutaneous Squamous Cell Carcinoma. Asia-Pacific Journal of Clinical Oncology.
2018;16(2).
PD-L1 positivity and relation with clinicopathological characteristics in head and neck squamous cell carcinoma patients
Year 2025,
Volume: 42 Issue: 4, 411 - 416, 31.12.2025
Berkan Düzgün
,
Özgür Kemal
,
Yasemin Kemal
,
Seda Gün
,
Emre Demirel
Abstract
Programmed death ligand 1 (PD-L1) is a transmembrane protein expressed on various immune cells including antigen-presenting cells, monocytes, macrophages, activated T and B lymphocytes, as well as on different tumour cells. It plays a role in weakening the T-cell-specific immune response, thereby allowing tumour cells to evade immune surveillance. This study aimed to evaluate PD-L1 expression in tumour tissue and the tumour microenvironment in patients diagnosed with head and neck squamous cell carcinoma (HNSCC), and to explore its association with clinicopathological features. A total of 68 paraffin-embedded tumour samples from surgically treated HNSCC patients were analyzed. PD-L1 immunohistochemical staining patterns, both cytoplasmic and membranous, were assessed in tumour cells and tumour-infiltrating lymphocytes (TILs). Statistical analysis was conducted to investigate the relationship between PD-L1 expression and variables such as age, gender, smoking history, perineural and lymphovascular invasion, tumour stage, and tumour grade. No PD-L1 staining was observed in tumour cells; however, PD-L1 expression was found to be prominent in peritumoral lymphocytes. Among the evaluated clinicopathological parameters, only lymph node metastasis showed a statistically significant correlation with PD-L1 positivity. These findings suggest that while PD-L1 is not expressed in tumour cells of HNSCC, its presence in the tumour microenvironment, particularly in peritumoral lymphocytes, may have clinical relevance. Further large-scale studies are warranted to better understand the implications of PD-L1 expression in HNSCC.
Ethical Statement
This study received approval from the Ondokuz Mayıs University Clinical Research Ethics Committee, dated 28/09/2018, with reference number OMU-KAEK 2018/302.
References
-
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
-
Marur S, Forastiere AA. Head and neck cancer: changing epidemiology, diagnosis, and treatment. Mayo Clin Proc.
2008;83(4):489-501.
-
Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, et al. Platinum-based chemotherapy plus
cetuximab in head and neck cancer. N Engl J Med. 2008;359(11):1116-27.
-
Machiels JP, René Leemans C, Golusinski W, Grau C, Licitra L, Gregoire V. Squamous cell carcinoma of the oral
cavity, larynx, oropharynx and hypopharynx: EHNS-ESMO-ESTRO Clinical Practice Guidelines for diagnosis,
treatment and follow-up. Ann Oncol. 2020;31(11):1462-75.
-
Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol.
2008;26:677-704.
-
Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T-cell
apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793-800.
-
Qiao XW, Jiang J, Pang X, Huang MC, Tang YJ, Liang XH, et al. The Evolving Landscape of PD-1/PD-L1 Pathway in
Head and Neck Cancer. Front Immunol. 2020;11:1721.
-
Lenouvel D, González-Moles M, 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 Oncol. 2020;106:104722.
-
Mishra PS, Sidhu A, Dwivedi G, Mulajker DS, Awasthi S. Determining PD-L1 expression in head and neck squamous
cell carcinoma using immunohistochemistry. Indian J Cancer. 2022;59(4):474-9.
-
Ferris RL. Immunology and Immunotherapy of Head and Neck Cancer. J Clin Oncol. 2015;33(29):3293-304.
-
Sanchez-Canteli M, Granda-Díaz R, Del Rio-Ibisate N, Allonca E, López-Alvarez F, Agorreta J, et al. PD-L1 expression
correlates with tumor-infiltrating lymphocytes and better prognosis in patients with HPV-negative head and neck
squamous cell carcinomas. Cancer Immunol Immunother. 2020;69(10):2089-100.
-
Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G, Jr., et al. Pembrolizumab alone or with
chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the
head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019;394(10212):1915-28.
-
Ou D, Adam J, Garberis I, Blanchard P, Nguyen F, Levy A, et al. Clinical relevance of tumor infiltrating lymphocytes,
PD-L1 expression and correlation with HPV/p16 in head and neck cancer treated with bio- or chemo-radiotherapy.
Oncoimmunology. 2017;6(9):e1341030.
-
Lenouvel D, González-Moles M, Ruiz-Ávila I, Chamorro-Santos C, González-Ruiz L, González-Ruiz I, et al.
Clinicopathological and prognostic significance of PD-L1 in oral cancer: A preliminary retrospective
immunohistochemistry study. Oral Dis. 2021;27(2):173-82.
-
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(1):152768.
-
Malik IS, Asif M, Bashir N, Ara N, Rashid F, Din HU, et al. Frequency of Expression of PD-1 andPD-L1 in Head and Neck
Squamous Cell Carcinoma and Their Association With Nodal Metastasis: A Cross-Sectional Study. Asian Pacific
Journal of Cancer Prevention. 2022;23(2):467-73.
-
Moratin J, Metzger K, Safaltin A, Herpel E, Hoffmann J, Freier K, et al. Upregulation of PD‐L1 and PD‐L2 in Neck Node
Metastases of Head and Neck Squamous Cell Carcinoma. Head & Neck. 2019;41(8):2484-91.
-
Kamiya S, Kato J, Kamiya T, Yamashita T, Sumikawa Y, Hida T, et al. Association Between PD‐L1 Expression and
Lymph Node Metastasis in Cutaneous Squamous Cell Carcinoma. Asia-Pacific Journal of Clinical Oncology.
2018;16(2).