Article Data

  • Views 969
  • Dowloads 160

Original Research

Open Access

Expressions of PD-L1 and FOXP3 in uterine cervical neoplasms may indicate tumor invasion and squamous differentiation

  • Sevil Sayhan1
  • Gulden Diniz2,*,
  • Duygu Ayaz1
  • Dudu Solakoglu Kahraman1

1Pathology Laboratory, SBU İzmir Tepecik Education and Research Hospital, 35020 İzmir, Turkey

2Department of Pathology, İzmir Democracy University, 35140 İzmir, Turkey

DOI: 10.31083/j.ejgo4204116 Vol.42,Issue 4,August 2021 pp.769-774

Submitted: 12 November 2020 Accepted: 09 April 2021

Published: 15 August 2021

*Corresponding Author(s): Gulden Diniz E-mail: gulden.diniz@idu.edu.tr agdiniz@gmail.com

Abstract

Objectives: Increasing evidence has demonstrated that upregulation of programmed death cell ligand-1 (PD-L1) and FOXP3-positive regulatory T cells in different malignancies plays a critical role in tumor progression. In the present study, the evaluation of PD-L1 and FOXP3 tissue expressions in a spectrum of cervical neoplasms were performed. Material and method: Immunohistochemical PD-L1 and FOXP3 expressions were evaluated in a total of 107 formalin-fixed, paraffin-embedded uterine cervical neoplasm specimens, and their association with some pathological parameters was tried to be elucidated. Results: Cases with low or high squamous intraepithelial lesion (n = 59), squamous cell carcinoma (n = 27), adenosquamous carcinoma (n = 15) and adenocarcinoma (n = 6) were included in this study. Tumoral PD-L1 was detected in most squamous cell carcinomas while it was found in almost none of the intraepithelial lesions (p < 0.001). Similarly, the number of both PD-L1, and FOXP3-positive inflammatory cells was statistically significantly higher in invasive tumors than in intraepithelial lesions (p < 0.001). Conclusion: Our findings demonstrated the association between the histological types of uterine neoplasms and PD-L1 or FOXP expressions, as well as the correlation between presence of invasion and tumoral PD-L1 expression. Therefore, it may be suggested that PD-L1 plays an important role in the pathogenesis of cervical neoplasms.


Keywords

Uterus; Cervical carcinomas; Squamous intraepithelial lesions; PD-L1; FOXP3

Cite and Share

Sevil Sayhan,Gulden Diniz,Duygu Ayaz,Dudu Solakoglu Kahraman. Expressions of PD-L1 and FOXP3 in uterine cervical neoplasms may indicate tumor invasion and squamous differentiation. European Journal of Gynaecological Oncology. 2021. 42(4);769-774.

References

[3] Degirmenci M, Diniz G, Solakoglu Kahraman D, Sayhan S, Oksuz P, Ayaz D, et al. Evaluation of the Caveolin-1 expressions in uterine cervical carcinomas. European Journal of Gynaecological Oncology. 2017; 38: 785–789.

[4] Lei J, Andrae B, Ploner A, Lagheden C, Eklund C, Nordqvist Kleppe S, et al. Cervical screening and risk of adenosquamous and rare histological types of invasive cervical carcinoma: population based nested case-control study. BMJ. 2019; 365: l1207.

[5] Cosper PF, McNair C, González I, Wong N, Knudsen KE, Chen JJ, et al. Decreased local immune response and retained HPV gene expression during chemoradiotherapy are associated with treatment resistance and death from cervical cancer. International Journal of Cancer. 2020; 146: 2047–2058.

[6] Wing JB, Tanaka A, Sakaguchi S. Human FOXP3+ regulatory t cell heterogeneity and function in autoimmunity and cancer. Immunity. 2019; 50: 302–316.

[7] Li Z, Dong P, Ren M, Song Y, Qian X, Yang Y, et al. PD-L1 expression is associated with tumor FOXP3+ regulatory T-cell infiltration of breast cancer and poor prognosis of patient. Journal of Cancer. 2016; 7: 784–793.

[8] Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJM, Robert L, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014; 515: 568–571.

[9] Shen LS, Wang J, Shen DF, Yuan XL, Dong P, Li MX, et al. CD4(+) CD25(+) CD127 (low/-) regulatory T cells Express Foxp3 and su-press effector T cell proliferation and contribute to gastric cancers progression. Clinical Immunology. 2009; 131: 109–118.

[10] Kahraman DS, Diniz G, Sayhan S, Sayar C, Ayaz D, Gokcu M, Karadeniz T. The prognostic significance of PD-L1 and foxp3 expressions in tumor cells and the tumor microenvironment of ovarian epithelial tumors. International Journal of Clinical and Experimental Pathology. 2018; 11: 3884–3890.

[11] Thompson ED, Zahurak M, Murphy A, Cornish T, Cuka N, Abdelfatah E, et al. Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma. Gut. 2017; 66: 794–801.

[12] van den Ende T, van den Boorn HG, Hoonhout NM, van Etten-Jamaludin FS, Meijer SL, Derks S, et al. Priming the tumor immune microenvironment with chemo(radio)therapy: a systematic review across tumor types. Biochimica et Biophysica Acta (BBA)—Reviews on Cancer. 2020; 1874: 188386.

[13] Chinai JM, Janakiram M, Chen F, Chen W, Kaplan M, Zang X. New immunotherapies targeting the PD-1 pathway. Trends in Pharmacological Sciences. 2015; 36: 587–595.

[14] Brahmer JR, Tykodi SS, Chow LQM, Hwu W, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. The New England Journal of Medicine. 2012; 366: 2455–2465.

[15] Zhang M, Dong Y, Liu H, Wang Y, Zhao S, Xuan Q, et al. The clinicopathological and prognostic significance of PD-L1 expression in gastric cancer: a meta-analysis of 10 studies with 1,901 patients. Scientific Reports. 2016; 6: 37933.

[16] Choi E, Chang MS, Byeon S, Jin H, Jung KC, Kim H, et al. Prognos-tic perspectives of PD-L1 combined with tumor-infiltrating lymphocytes, Epstein-Barr virus, and microsatellite instability in gastric carcinomas. Diagnostic Pathology. 2020; 15: 69.

[17] Saito H, Kono Y, Murakami Y, Shishido Y, Kuroda H, Matsunaga T, et al. Highly Activated PD-1/PD-L1 Pathway in Gastric Cancer with PD-L1 Expression. Anticancer Research. 2018; 38: 107–112.

[18] Droeser RA, Hirt C, Viehl CT, Frey DM, Nebiker C, Huber X, et al. Clinical impact of programmed cell death ligand 1 expression in colorectal cancer. European Journal of Cancer. 2013; 49: 2233–2242.

[19] Koh J, Hur JY, Lee KY, Kim MS, Heo JY, Ku BM, et al. Regulatory (FoxP3(+)) T cells and TGF-beta predict the response to anti-PD-1 immunotherapy in patients with non-small cell lung cancer. Scientific Reports. 2020; 10: 18994.

[20] Francisco LM, Salinas VH, Brown KH, Vanguri VK, Freeman GJ; Kuchroo VK, et al. PD-L1 regulates the development, mainte-nance, and function of induced regulatory T cells. Journal of Experimental Medicine. 2009; 206: 3015–3129.

[21] Kamada T, Togashi Y, Tay C, Ha D, Sasaki A, Nakamura Y, et al. PD-1+ regulatory T cells amplified by PD-1 blockade promote hyperprogression of cancer. Proceedings of the National Academy of Sciences. 2019; 116: 9999–10008.

[22] Kashima J, Okuma Y. Harmonization study of antibodies and platforms for programmed death ligand 1 immunostaining in non-small cell lung cancer: does shuffling couples settle the troubles?Journal of Thoracic Disease. 2018; 10: S2124–S2126.

[23] Ozgur HH, Ercetin AP, Eliyatkin N, Seren A, Kupelioglu A, Ortac R, et al. Regulatory T cells and their prognostic value in hepatopancreatobiliary tumours. Hepato-Gastroenterology. 2014; 61: 1847–1851.

[24] Taube JM, Klein A, Brahmer JR, Xu H, Pan X, Kim JH, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clinical Cancer Research. 2014; 20: 5064–5074.

[25] Turcotte S, Gros A, Tran E, Lee CR, Wunderlich JR, Robbins PF, et al. Tumor-reactive CD8+ T cells in metastatic gastrointestinal cancer refractory to chemotherapy. Clinical Cancer Research. 2014; 20: 331–343.

[26] Lin B, Du L, Li H, Zhu X, Cui L, Li X. Warriors fight against tumors powerfully. Biomed Pharmacother. 2020; 132: 110873.

[27] Ring KL, Yemelyanova AV, Soliman PT, Frumovitz MM, Jazaeri AA. Potential immunotherapy targets in recurrent cervical cancer. Gynecologic Oncology. 2017; 145: 462–468.

[28] Heeren AM, Punt S, Bleeker MC, Gaarenstroom KN, van der Velden J, Kenter GG, et al. Prognostic effect of different PD-L1 expression patterns in squamous cell carcinoma and adenocarcinoma of the cervix. Modern Pathology. 2016; 29: 753–763.

[29] Tsuchiya T, Someya M, Takada Y, Hasegawa T, Kitagawa M, Fukushima Y, et al. Association between radiotherapy-induced alteration of programmed death ligand 1 and survival in patients with uterine cervical cancer undergoing preoperative radiotherapy. Strahlentherapie Und Onkologie. 2020; 196: 725–735.

[30] Lippens L, Van Bockstal M, De Jaeghere EA, Tummers P, Makar A, De Geyter S, et al. Immunologic impact of chemoradiation in cervical cancer and how immune cell infiltration could lead toward personalized treatment. International Journal of Cancer. 2020; 147: 554–564.

[31] Grochot RM, Brollo J, Neto FR, Tregnago AC, Scholze C, Norris R, et al. Expression of PD-L1 in cervical carcinoma and its impact on survival associated with T-cell infiltration and FoxP3 expression. Cancer Management and Research. 2019; 11: 4597–4605.

[32] Liang Y, Lü W, Zhang X, Lü B. Tumor-infiltrating CD8+ and FOXP3+ lymphocytes before and after neoadjuvant chemotherapy in cervical cancer. Diagnostic Pathology. 2018; 13: 93.

[33] Stevanović S, Helman SR, Wunderlich JR, Langhan MM, Doran SL, Kwong MLM, et al. A phase II study of tumor-infiltrating lymphocyte therapy for human papillomavirus—associated epithelial cancers. Clinical Cancer Research. 2019; 25: 1486–1493.

Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time

Conferences

Top