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Expression of Programmed Death-Ligand 1 in Laryngeal Carcinoma and its Effects on Immune Cell Subgroup Infiltration

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Pathology & Oncology Research

Abstract

To study the expression of programmed death-ligand 1 (PD-L1), and its effects on CD8+ tumor infiltrating lymphocytes (TILs) and tumor associated macrophages (TAMs) in human laryngeal squamous cell carcinoma. Sixty-nine patients with laryngeal carcinoma and 10 with vocal cord leukoplakia received tumor resection at Neck Surgery Department in the Second Affiliation Hospital of Jilin University (Changchun, Jilin) from Jan. 2010 to Dec. 2015. The expressions of PD-L1, CD8, CD16 and CD206 in laryngeal carcinoma, paracancerous and vocal cord leukoplakia tissues were detected with immunohistochemistry. The associations between PD-L1 expression and clinicopathologic features, expression of TAMs and CD8+ T cell infiltration were analyzed. Expression of PD-L1 is significantly higher in laryngeal carcinoma than in paracancerous or leukoplakia tissue. The expression of PD-L1 is closely associated with stage of laryngeal cancer, histological differentiation and neck lymphatic metastasis. PD-L1 expression is negatively correlated with the number of CD8+ TILs and CD16+ cells (M1 type TAMs), while is positively associated with CD206+ (M2 type TAMs). PD-L1 is highly expressed in the laryngeal cancer with the tumor microenvironment immunosuppression.

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References

  1. Ferris RL, Whiteside TL, Ferrone S (2006) Immune escape associated with functional defects in antigen-processing machinery in head and neck cancer. Clin Cancer Res 12(13):3890–3895

    Article  CAS  Google Scholar 

  2. Zandberg DP, Strome SE (2014) The role of the PD-L1:PD-1 pathway in squamous cell carcinoma of the head and neck. Oral Oncol 50(7):627–632

    Article  CAS  Google Scholar 

  3. Jinushi M, Komohara Y (2015) Tumor-associated macrophages as an emerging target against tumors: creating a new path from bench to bedside. Biochim Biophys Acta 1855(2):123–130

    CAS  Google Scholar 

  4. Lee YH, Martin-Orozco N, Zheng P, Li J, Zhang P, Tan H, Park HJ, Jeong M, Chang SH, Kim BS, Xiong W, Zang W, Guo L, Liu Y, Dong ZJ, Overwijk WW, Hwu P, Yi Q, Kwak L, Yang Z, Mak TW, Li W, Radvanyi LG, Ni L, Liu D, Dong C (2017) Inhibition of the B7-H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function. Cell Res 27:1034–1045

    Article  CAS  Google Scholar 

  5. Liu Z, Zhao Y, Fang J, Cui R, Xiao Y et al (2017) SHP2 negatively regulates HLA-ABC and PD-L1 expression via STAT1 phosphorylation in prostate cancer cells. Oncotarget

  6. Fife BT, Pauken KE, Eagar TN, Obu T, Wu J, Tang Q, Azuma M, Krummel MF, Bluestone JA (2009) Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nat Immunol 10(11):1185–1192

    Article  CAS  Google Scholar 

  7. Zhang L, Li Z, Ding G, La X, Yang P et al (2017) GRP78 plays an integral role in tumor cell inflammation-related migration induced by M2 macrophages. Cell Signal 37:136–148

    Article  CAS  Google Scholar 

  8. Chen J, Li G, Meng H, Fan Y, Song Y, Wang S, Zhu F, Guo C, Zhang L, Shi Y (2012) Upregulation of B7-H1 expression is associated with macrophage infiltration in hepatocellular carcinomas. Cancer Immunol Immunother 61(1):101–108

    Article  Google Scholar 

  9. Gordon SR, Maute RL, Dulken BW, Hutter G, George BM, McCracken MN, Gupta R, Tsai JM, Sinha R, Corey D, Ring AM, Connolly AJ, Weissman IL (2017) PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature 545(7655):495–499

    Article  CAS  Google Scholar 

  10. Francisco LM, Salinas VH, Brown KE, Vanguri VK, Freeman GJ, Kuchroo VK, Sharpe AH (2009) PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med 206(13):3015–3029

    Article  CAS  Google Scholar 

  11. Yvorel V, Patoir A, Casteillo F, Tissot C, Fournel P, Stachowicz ML, Karpathiou G, Tiffet O, Péoc’h M, Forest F (2017) PD-L1 expression in pleomorphic, spindle cell and giant cell carcinoma of the lung is related to TTF-1, p40 expression and might indicate a worse prognosis. PLoS One 12(7):e0180346

    Article  Google Scholar 

  12. Roper E, Lum T, Palme CE, Ashford B, Ch'ng S, Ranson M, Boyer M, Clark J, Gupta R (2017) PD-L1 expression predicts longer disease free survival in high risk head and neck cutaneous squamous cell carcinoma. Pathology 49:499–505

    Article  CAS  Google Scholar 

  13. Milstein O, Hagin D, Lask A, Reich-Zeliger S, Shezen E, Ophir E, Eidelstein Y, Afik R, Antebi YE, Dustin ML, Reisner Y (2011) CTLs respond with activation and granule secretion when serving as targets for T-cell recognition. Blood 117(3):1042–1052

    Article  CAS  Google Scholar 

  14. Mischinger J, Comperat E, Schwentner C, Stenzl A, Gakis G (2015) Inflammation and Cancer: what can we therapeutically expect from checkpoint inhibitors? Curr Urol Rep 16(9):59

    Article  Google Scholar 

  15. Ager CR, Reilley MJ, Nicholas C, Bartkowiak T, Jaiswal AR, Curran MA (2017) Intratumoral STING activation with T cell checkpoint modulation generates systemic antitumor immunity. Cancer Immunol Res 5:676–684

    Article  CAS  Google Scholar 

  16. Fujii N, Shomori K, Shiomi T, Nakabayashi M, Takeda C, Ryoke K, Ito H (2012) Cancer-associated fibroblasts and CD163-positive macrophages in oral squamous cell carcinoma: their clinicopathological and prognostic significance. J Oral Pathol Med 41(6):444–451

    Article  Google Scholar 

  17. Chen C, Qu QX, Shen Y, Mu CY, Zhu YB, Zhang XG, Huang JA (2012) Induced expression of B7-H4 on the surface of lung cancer cell by the tumor-associated macrophages: a potential mechanism of immune escape. Cancer Lett 317(1):99–105

    Article  CAS  Google Scholar 

  18. Kuang DM, Zhao Q, Peng C, Xu J, Zhang JP, Wu C, Zheng L (2009) Activated monocytes in peritumoral stroma of hepatocellular carcinoma foster immune privilege and disease progression through PD-L1. J Exp Med 206(6):1327–1337

    Article  CAS  Google Scholar 

  19. Kang FB, Wang L, Li D, Zhang YG, Sun DX (2015) Hepatocellular carcinomas promote tumor-associated macrophage M2-polarization via increased B7-H3 expression. Oncol Rep 33(1):274–282

    Article  CAS  Google Scholar 

  20. Chen W, Jiang J, Xia W, Huang J (2017) Tumor-related exosomes contribute to tumor-promoting microenvironment: an immunological perspective. J Immunol Res 2017:1073947

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Thanks to Dr. Xueshibojie Liu and Yuanzhang Zu for their contribution to the work!

Funding

This work is supported by the National Natural Science Youth Foundation of China (81502348), the National Natural Science Foundation of China (81572653), International Cooperation Project from Science and Technology Department of Jilin Province (20180414054GH) and the Natural Science Foundation of Jilin Province (20160101039JC).

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Authors and Affiliations

  1. Department of Otolaryngology Head and Neck Surgery, The Second Hospital, Jilin University, No. 218 Ziqiang Street, Changchun, 130041, China

    Dan Yu, Jinzhang Cheng, Kai Xue, Xue Zhao, Lianji Wen & Chengbi Xu

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  1. Dan Yu
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  2. Jinzhang Cheng
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  3. Kai Xue
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  4. Xue Zhao
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  5. Lianji Wen
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  6. Chengbi Xu
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Correspondence to Chengbi Xu.

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Yu, D., Cheng, J., Xue, K. et al. Expression of Programmed Death-Ligand 1 in Laryngeal Carcinoma and its Effects on Immune Cell Subgroup Infiltration. Pathol. Oncol. Res. 25, 1437–1443 (2019). https://doi.org/10.1007/s12253-018-0501-x

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  • DOI: https://doi.org/10.1007/s12253-018-0501-x

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