Prognostic Significance of PD-L1 and mTOR Expression in Oral Squamous Cell Carcinoma

Authors

  • Nattinee Charoen Department of Pathology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand
  • Kitti Jantharapattana Department of Otolaryngology Head and Neck Surgery, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand
  • Paramee Thongsuksai Department of Pathology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand

DOI:

https://doi.org/10.31584/jhsmr.2020745

Keywords:

oral squamous cell carcinoma, PD-L1, mTOR, prognosis

Abstract

Objective: Programmed cell death ligand 1 (PD-L1) and mammalian target of rapamycin (mTOR) are key players in host immune evasion and oncogenic activation, respectively. Evidence of the prognostic role in oral squamous cell carcinoma (OSCC) is conflicting. This study examined the associations of PD-L1 and mTOR expression with 5-year overall survival in OSCC patients.
Material and Methods: The expressions of PD-L1 and mTOR proteins were immunohistochemically evaluated on tissue microarrays of 191 patients with OSCC who were treated by surgery at Songklanagarind Hospital, Thailand from 2008 to 2011. Cox regression analysis was used to determine independent prognostic factors.
Results: PD-L1 expression was observed in 14.1% of cases while mTOR expression was present in 74.3% of cases. Females were more likely to have tumors with PD-L1 (p-value=0.007) and mTOR expressions (p-value=0.003) than males. In addition, lower clinical stage and well differentiated tumor are more likely to have mTOR expression (p-value= 0.038 and p-value<0.001, respectively). Cox regression analysis showed that age, tumor stage, nodal stage, combined surgical treatment with radiation or chemoradiation therapy, surgical margin status, PD-L1 expression and mTOR expression are independent prognostic factors. High PD-L1 expression (hazard ratio (HR) 3.14, 95% confidence interval (CI), 1.26–7.79) and high mTOR expression (HR 1.69, 95% CI, 1.00–2.84) are strong predictors of poor outcome.
Conclusion: A proportion of OSCC expressed PD-L1 and mTOR proteins. Expression of PD-L1 and mTOR proteins are strong prognostic factors of OSCC.

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;68:394-424.

Carvalho AL, Ikeda MK, Magrin J, Kowalski LP. Trends of oral and oropharyngeal cancer survival over five decades in 3267 patients treated in a single institution. Oral Oncol 2004;40:71-6.

Pruegsanusak K, Peeravut S, Leelamanit V, Sinkijcharoenchai W, Jongsatitpaiboon J, Phungrassami T. Survival and prognostic factors of different sites of head and neck cancer: an analysis from Thailand. Asian Pac J Cancer Prev 2012;13:885-90.

Chen TC, Hsu CW, Lou PJ, Ko JY, Yang TL, Chen CN, et al. The clinical predictive factors for subsequent distant metastasis in patients with locoregionally advanced oral squamous cell carcinoma. Oral Oncol 2013;49:367-73.

Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 2012;366: 2455-65.

Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, andimmune correlates of anti-PD-1 antibody in cancer. N Engl J Med 2012;366: 2443-54.

Riley JL. PD-1 signaling in primary T cells. Immunol Rev 2009; 229:114-25.

Sanmamed MF, Chen L. Inducible expression of B7-H1 (PD-L1) and its selective role in tumor site immune modulation. Cancer J 2014;20:256-61.

Sul J, Blumenthal GM, Jiang X, He K, Keegan P, Pazdur R. FDA approval summary: pembrolizumab for the treatment of patients with metastatic non-small cell lung cancer whose tumors express programmed death-ligand 1. Oncologist 2016; 21:643-50.

Muenst S, Schaerli AR, Gao F, Däster S, Trella E, Droeser RA, et al. Expression of programmed deathligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat 2014;146:15-24.

Leite KR, Reis ST, Junior JP, Zerati M, Gomes Dde O, Camara Lopes LH, et al. PD-L1 expression in renal cell carcinoma clear cell type is related to unfavorable prognosis. Diagn Pathol 2015; 10:189.

Zeng J, Zhang XK, Chen HD, Zhong ZH, Wu QL, Lin SX. Expression of programmed cell death-ligand 1 and its correlation with clinical outcomes in gliomas. Oncotarget 2016;7:8944-55.

Lin YM, Sung WW, Hsieh MJ, Tsai SC, Lai HW, Yang SM, et al. High PD-L1 expression correlates with metastasis and poor prognosis in oral squamous cell carcinoma. PLoS One 2015;10. doi: 10.1371/journal.pone.0142656.

Müller T, Braun M, Dietrich D, Aktekin S, Höft S, Kristiansen G, et al. PD-L1: a novel prognostic biomarker in head and neck squamous cell carcinoma. Oncotarget 2017;8:52889-900.

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.

Hanna GJ, Woo SB, Li YY, Barletta JA, Hammerman PS, Lorch JH. Tumor PD-L1 expression is associated with improved survival and lower recurrence risk in young women with oral cavity squamous cell carcinoma. Int J Oral Maxillofac Surg 2018;47:568-77.

Menon S, Manning BD. Common corruption of the mTOR signaling network in human tumors. Oncogene 2008;27 (Suppl 2):S43-51.

Ocana A, Vera-Badillo F, Al-Mubarak M, Templeton AJ, Corrales-Sanchez V, Diez-Gonzalez L, et al. Activation of the PI3K/mTOR/AKT pathway and survival in solid tumors: systematic review and meta-analysis. PLoS One 2014;9. doi: 10.1371/journal.pone.0095219.

Marques AE, Elias ST, Porporatti AL, Castilho RM, Squarize CH, De Luca Canto G, et al. mTOR pathway protein immunoexpression as a prognostic factor for survival in head and neck cancer patients: a systematic review and meta-analysis. J Oral Pathol Med 2016;45:319-28.

Meric-Bernstam F, Gonzalez-Angulo AM. Targeting the mTOR signaling network for cancer therapy. J Clin Oncol 2009;27: 2278-87.

Wang Z, Valera JC, Zhao X, Chen Q, Gutkind JS. mTOR co-targeting strategies for head and neck cancer therapy. Cancer Metastasis Rev 2017;36:491-502.

Wangmo C, Charoen N, Jantharapattana K, Dechaphunkul A, Thongsuksai P. Epithelial-mesenchymal transition predicts survival in oral squamous cell carcinoma. Pathol Oncol Res 2019. doi: 10.1007/s12253-019-00731-z.

Cho YA, Yoon HJ, Lee JI, Hong SP, Hong SD. Relationship between the expressions of PD-L1 and tumor-infiltrating lymphocytes in oral squamous cell carcinoma. Oral Oncol 2011; 47:1148-53.

Ngamphaiboon N, Chureemas T, Siripoon T, Arsa L, Trachu N, Jiarpinitnun C, et al. Characteristics and impact of programmed death-ligand 1 expression, CD8+ tumor-infiltrating lymphocytes, and p16 status in head and neck squamous cell carcinoma. Med Oncol 2019;36:21.

Büttner R, Gosney JR, Skov BG, Adam J, Motoi N, Bloom KJ, et al. Programmed death-ligand 1 immunohistochemistry testing: a review of analytical assays and clinical implementation in non-small-cell lung cancer. J Clin Oncol 2017;35:3867- 76.

Mattox AK, Lee J, Westra WH, Pierce RH, Ghossein R, Faquin WC, et al. PD-L1 expression in head and neck squamous cell carcinomas derives primarily from functionally anergic CD4(+) TILs in the presence of PD-L1 (+) TAMs. Cancer Res 2017;77: 6365-74.

Oliveira-Costa JP, de Carvalho AF, da Silveira da GG, Amaya P, Wu Y, Park KJ, et al. Gene expression patterns through oral squamous cell carcinoma development: PD-L1 expression in primary tumor and circulating tumor cells. Oncotarget 2015; 6:20902-20.

Ahn H, Yang JM, Kim H, Chung JH, Ahn SH, Jeong WJ, et al. Clinicopathologic implications of the miR-197/ PD-L1 axis in oral squamous cell carcinoma. Oncotarget 2017;8: 66178-94.

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. doi: 10.1111/cpr.12537.

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;41:2484-91.

Pedrero JM, Carracedo DG, Pinto CM, Zapatero AH, Rodrigo JP, Nieto CS, et al. Frequent genetic and biochemical alterations of the PI 3-K/AKT/PTEN pathway in head and neck squamous cell carcinoma. Int J Cancer 2005;114:242-8.

Martins F, de Sousa SC, Dos Santos E, Woo SB, Gallottini M. PI3K-AKT-mTOR pathway proteins are differently expressed in oral carcinogenesis. J Oral Pathol Med 2016;45: 746-52.

Monteiro LS, Delgado ML, Ricardo S, Garcez F, do Amaral B, Warnakulasuriya S, et al. Phosphorylated mammalian target of rapamycin is associated with an adverse outcome in oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol 2013;115:638-45.

Naruse T, Yanamoto S, Yamada S, Rokutanda S, Kawakita A, Kawasaki G, et al. Anti-tumor effect of the mammalian target of rapamycin inhibitor everolimus in oral squamous cell carcinoma. Pathol Oncol Res 2015;21:765-73.

Li SH, Chien CY, Huang WT, Luo SD, Su YY, Tien WY, et al. Prognostic significance and function of mammalian target of rapamycin in tongue squamous cell carcinoma Sci Rep 2017; 7:8178.

Okkenhaug K. Signaling by the phosphoinositide 3-kinase family in immune cells. Annu Rev Immunol 2013;31:675-704.

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Published

2020-06-02

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Charoen N, Jantharapattana K, Thongsuksai P. Prognostic Significance of PD-L1 and mTOR Expression in Oral Squamous Cell Carcinoma. J Health Sci Med Res [Internet]. 2020 Jun. 2 [cited 2024 Dec. 23];38(4):255-66. Available from: https://he01.tci-thaijo.org/index.php/jhsmr/article/view/242967

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