Expression of PD-L1 and Relationship with Tumor-Infiltrating Lymphocytes and Metastasis in Serous Ovarian Carcinoma.

Authors

  • Riadi Department of Anatomical Pathology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
  • Rina Masadah Department of Anatomical Pathology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia
  • Berti J. Nelwan Department of Anatomical Pathology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

Keywords:

PD-L1, Ovarian Cancer, LGSC, HGSC, Metastasis, TILs

Abstract

Ovarian serous carcinoma is the most common ovarian malignancy in women, and most of them are diagnosed at an advanced stage and have metastasis. With current therapy, the 5-year mean survival rate is still not satisfying and opening a new approach. Immunotherapy using anti-PD-L1 is widely used in various types of malignancies. The use of PD-L1 in serous ovarian carcinoma is still quite limited. This study aimed to explore the potential of immunotherapy by assessing the expression of PD-L1 in serous ovarian carcinoma. Immunohistochemical performed to analyze PD-L1 dan compared with metastases incidence and tumor immune response. PD-L1 expression appeared to be stronger in high-grade serous carcinoma than low-grade serous carcinoma, but there was no statistical difference (p 0.539). There was a correlation between PD-L1 and metastasis incident (p 0.015) in high-grade serous ovarian carcinoma. There was a significant correlation between PD-L1 and tumor-infiltrating lymphocytes. PD-L1 in serous carcinoma has a strong relationship with TILs, opens up the possibilities of using anti-PD-L1 on serous carcinoma. PD-L1 expression in high-grade serous carcinoma has a relationship with the incidence of metastases.

References

. Z. Momenimovahed, A. Tiznobaik, S. Taheri, and H. Salehiniya, “Ovarian cancer in the world: Epidemiology and risk factors,” Int. J. Womens. Health, vol. 11, pp. 287–299, 2019, doi: 10.2147/IJWH.S197604.

. F. De Felice et al., “Immunotherapy of Ovarian Cancer: The Role of Checkpoint Inhibitors,” J. Immunol. Res., vol. 2015, 2015, doi: 10.1155/2015/191832.

. J. Ferlay et al., “Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods,” Int. J. Cancer, vol. 144, no. 8, pp. 1941–1953, Apr. 2019, doi: https://doi.org/10.1002/ijc.31937.

. B. M. Reid, J. B. Permuth, and T. A. Sellers, “Epidemiology of ovarian cancer: a review,” Cancer Biol. Med., vol. 14, no. 1, pp. 9–32, 2017, doi: 10.20892/j.issn.2095-3941.2016.0084.

. Y. Liu et al., “Relationship between initiation time of adjuvant chemotherapy and survival in ovarian cancer patients: A dose-response meta-analysis of cohort studies,” Sci. Rep., vol. 7, no. 1, pp. 1–8, 2017, doi: 10.1038/s41598-017-10197-1.

. T. D.S., A. R., and K. S.B., “Mechanisms of transcoelomic metastasis in ovarian cancer,” Lancet Oncol., vol. 7, no. 11, pp. 925–934, 2006, [Online]. Available: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emed7&NEWS=N&AN=2006519275.

. P. Buderath et al., “Prognostic significance of PD-1 and PD-L1 positive tumor-infiltrating immune cells in ovarian carcinoma,” Int. J. Gynecol. Cancer, vol. 29, no. 9, pp. 1389–1395, 2019, doi: 10.1136/ijgc-2019-000609.

. J. L. Pautu and L. Kumar, “Intratumoral T cells and survival in epithelial ovarian cancer.,” Natl. Med. J. India, vol. 16, no. 3, pp. 150–151, 2003.

. W. T. Hwang, S. F. Adams, E. Tahirovic, I. S. Hagemann, and G. Coukos, “Prognostic significance of tumor-infiltrating T cells in ovarian cancer: A meta-analysis,” Gynecol. Oncol., vol. 124, no. 2, pp. 192–198, 2012, doi: 10.1016/j.ygyno.2011.09.039.

. L. Martin de la Fuente et al., “PD-1/PD-L1 expression and tumor-infiltrating lymphocytes are prognostically favorable in advanced high-grade serous ovarian carcinoma,” Virchows Arch., vol. 477, no. 1, pp. 83–91, 2020, doi: 10.1007/s00428-020-02751-6.

. J. R. Webb, K. Milne, D. R. Kroeger, and B. H. Nelson, “PD-L1 expression is associated with tumor-infiltrating T cells and favorable prognosis in high-grade serous ovarian cancer,” Gynecol. Oncol., vol. 141, no. 2, pp. 293–302, 2016, doi: 10.1016/j.ygyno.2016.03.008.

. W. Nhokaew, P. Kleebkaow, N. Chaisuriya, and C. Kietpeerakool, “Programmed death ligand 1 (PD-L1) expression in epithelial ovarian cancer: A comparison of type I and type II tumors,” Asian Pacific J. Cancer Prev., vol. 20, no. 4, pp. 1161–1169, 2019, doi: 10.31557/APJCP.2019.20.4.1161.

. R. Salgado et al., “The evaluation of tumor-infiltrating lymphocytes (TILS) in breast cancer: Recommendations by an International TILS Working Group 2014,” Ann. Oncol., vol. 26, no. 2, pp. 259–271, 2015, doi: 10.1093/annonc/mdu450.

. Q. Wang, W. Lou, W. Di, and X. Wu, “Prognostic value of tumor PD-L1 expression combined with CD8+ tumor infiltrating lymphocytes in high grade serous ovarian cancer,” Int. Immunopharmacol., vol. 52, no. July, pp. 7–14, 2017, doi: 10.1016/j.intimp.2017.08.017.

. J. Chen, C. C. Jiang, L. Jin, and X. D. Zhang, “Regulation of PD-L1: A novel role of pro-survival signalling in cancer,” Ann Oncol, vol. Jun, no. 27(6), pp. 1055–61, 2016.

. N. Yaghoubi, A. Soltani, K. Ghazvini, S. M. Hassanian, and S. I. Hashemy, “PD-1/ PD-L1 blockade as a novel treatment for colorectal cancer,” Biomed. Pharmacother., vol. 110, no. September 2018, pp. 312–318, 2019, doi: 10.1016/j.biopha.2018.11.105.

. W. Lin, M. Chen, L. Hong, H. Zhao, and Q. Chen, “Crosstalk between PD-1/PD-L1 blockade and its combinatorial therapies in tumor immune microenvironment: A focus on HNSCC,” Front. Oncol., vol. 8, no. NOV, pp. 1–16, 2018, doi: 10.3389/fonc.2018.00532.

. F. C. Santini and M. D. Hellmann, “PD-1/PD-L1 axis in lung cancer,” Physiol. Behav., vol. 176, no. 10, pp. 139–148, 2017, doi: 10.1097/PPO.0000000000000300.PD-1/PD-L1.

. J. J. Wang et al., “Infiltration of T cells promotes the metastasis of ovarian cancer cells via the modulation of metastasis-related genes and PD-L1 expression,” Cancer Immunol. Immunother., vol. 69, no. 11, pp. 2275–2289, 2020, doi: 10.1007/s00262-020-02621-9.

. R. Y. Huang, A. Francois, A. R. McGray, A. Miliotto, and K. Odunsi, “Compensatory upregulation of PD-1, LAG-3, and CTLA-4 limits the efficacy of single-agent checkpoint blockade in metastatic ovarian cancer,” Oncoimmunology, vol. 6, no. 1, 2017, doi: 10.1080/2162402X.2016.1249561.

. C. Xue et al., “Expression and prognostic value of PD-L1 and PD-L2 in ovarian cancer,” Transl. Cancer Res., vol. 8, no. 1, pp. 111–119, 2019, doi: 10.21037/tcr.2019.01.09.

. S. M. Hunter et al., “Molecular profiling of low grade serous ovarian tumours identifies novel candidate driver genes.,” Oncotarget, vol. 6, no. 35, pp. 37663–37677, Nov. 2015, doi: 10.18632/oncotarget.5438.

. Marta Brunetti, I. Panagopoulos, I. Kostolomov, B. Davidson, S. Heim, and F. Micci, “Mutation analysis and genomic imbalances of cells found in effusion fluids from patients with ovarian cancer,” Oncol. Lett., vol. 20, no. 3, pp. 2273–2279, 2020, doi: 10.3892/ol.2020.11782.

. A. A. Ahmed et al., “Driver mutations in TP53 are ubiquitous in high grade serous carcinoma of the ovary.,” J. Pathol., vol. 221, no. 1, pp. 49–56, May 2010, doi: 10.1002/path.2696.

. I. Zerdes, A. Matikas, J. Bergh, G. Z. Rassidakis, and T. Foukakis, “Genetic, transcriptional and post-translational regulation of the programmed death protein ligand 1 in cancer: biology and clinical correlations,” Oncogene, vol. 37, no. 34, pp. 4639–4661, 2018, doi: 10.1038/s41388-018-0303-3.

. P. Ritprajak and M. Azuma, “Intrinsic and extrinsic control of expression of the immunoregulatory molecule PD-L1 in epithelial cells and squamous cell carcinoma,” Oral Oncology, vol. 51, no. 3. Elsevier Ltd, pp. 221–228, Mar. 01, 2015, doi: 10.1016/j.oraloncology.2014.11.014.

. K. C. Strickland et al., “Association and prognostic significance of BRCA1/2-mutation status with neoantigen load, number of tumor-infiltrating lymphocytes and expression of PD-1/PD-L1 in high grade serous ovarian cancer,” Oncotarget, vol. 7, no. 12, pp. 13587–13598, 2016, doi: 10.18632/oncotarget.7277.

. D. Peter C. Fong, “Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer,” N. Engl. J. Med., vol. 366, no. 26, pp. 2443–2454, 2012, [Online]. Available: https://www.nejm.org/doi/pdf/10.1056/NEJMoa0900212?articleTools=true.

. J. M. Taube et al., “Colocalization of inflammatory response with B7-H1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape,” Sci. Transl. Med., vol. 4, no. 127, 2012, doi: 10.1126/scitranslmed.3003689.

. M. Rosso et al., “E-cadherin: A determinant molecule associated with ovarian cancer progression, dissemination and aggressiveness.,” PLoS One, vol. 12, no. 9, p. e0184439, 2017, doi: 10.1371/journal.pone.0184439.

. Z. Feng, “p53 regulation of the IGF-1/AKT/mTOR pathways and the endosomal compartment.,” Cold Spring Harb. Perspect. Biol., vol. 2, no. 2, p. a001057, Feb. 2010, doi: 10.1101/cshperspect.a001057.

Downloads

Published

2021-05-01

How to Cite

Riadi, Masadah, R. ., & Nelwan, B. J. . (2021). Expression of PD-L1 and Relationship with Tumor-Infiltrating Lymphocytes and Metastasis in Serous Ovarian Carcinoma. International Journal of Sciences: Basic and Applied Research (IJSBAR), 57(2), 162–170. Retrieved from https://www.gssrr.org/index.php/JournalOfBasicAndApplied/article/view/12539

Issue

Vol. 57 No. 2 (2021)

Section

Articles

License

Authors who submit papers with this journal agree to the following terms.