PD-L1 in Breast Cancers and its Prognostic Significance

Authors

  • Sayher Kazmi
  • Sumayyah Shawana
  • Nighat Jamal

DOI:

https://doi.org/10.51985/AUSB2062

Keywords:

Breast cancer, PD-L1, Prognosis

Abstract

Breast cancer is the most common malignancy in females globally. Various factors are responsible for its development
which include both genetic and hormonal causes. An important discovery is the role of the PD-1/PD-L1 axis in the
development of cancers. The PD-1-/PD-L1 pathway plays a part in allowing tumour cells escape from the host’s immune
response and hence permits the proliferation of tumour cells. PD-L1 expression has been observed in various breast cancers
at distinct levels such as in tissues and in blood. Different methods have been utilized for its detection including
immunohistochemistry, RNA sequencing and ELISA, amongst others. The results have been conflicting regarding the
expression of PD-L1 and the prognosis of breast cancer based on parameters such as overall survival and disease free
survival. Different immunotherapies have also emerged as a new modality to treat breast cancer. This review intends to
explore the prognostic significance of PD-L1 expression in breast cancers.

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.

Yousaf A, Mahmood S, Faraz R, Quader UA, Asif H, Atif A, et al . Annual Cancer Registry Report-2018, of the Shaukat Khanum Memorial Cancer Hospital & Research Center, Pakistan. 2018 (cited July 2019). pp 4-8. Available at https://shaukatkhanum.org.pk/wp-content/uploads /2019/07/acrr-2018.pdf

Lester S, Kumar V, Abbas AK, Aster JC. The Breast. Robbins and Cotran Pathologic Basis of Disease. 9the Elsevier 2015 1052-1070.

Goldblum JR, McKenney JK, Lamps LW, Myers JL. Breast. Rosai and Ackerman’s Surgical Pathology. 11the Elsevier; 2018 p 1492-1497

Perou CM, Sorlie T, Eisen MB, Rijn MV, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature 2000: 406 (6797);747-752

Jiang X, Wang J , Deng X ,Xiong F, Ge J, Xiang B, et al. Role of the tumor microenvironment in PDL1/PD-1-mediated tumor immune escape. . Molecular Cancer 2019. 18 (10) https://doi.org/10.1186/s12943-018-0928-4

Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992 Nov;11 (11):3887-95.

Yamazaki T, Akiba H, Iwai H, Matsuda H, Aoki M, Tanno Y, et al. Expression of programmed death 1 ligands by murine T cells and APC. J Immunol. 2002; 169: 5538–45

Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat. Med. 1999, 5 (12): 1365–9. doi:10.1038/70932

Dong H, Strome SE, Salomao DR, Hideto T, Hirano F, Flies DB, et al. Tumour associated B7-H1 promotes T cell apoptosis: A potential mechanism of immune evasion. Nat. Med 2002. 8 793-800

Callea M, Albiges L, Gupta M, Cheng CS, Genega ME, Fay PA, et al. Differential Expression of PD-L1 between Primary and Metastatic Sites in Clear-Cell Renal Cell Carcinoma. Cancer Immunol. Res. 2015. 3(10) 1158-1164 doi: 10.1158/2326-6066

Rashed HE, AbdelRahman AE, AbdelGawad M, Balata S, El Shabrawy M. Prognostic Significance of Programmed Cell Death Ligand 1 (PD-L1), CD8+ Tumour Infiltrating Lymphocytes and p53 in Non Small Cell Lung Cancer: An Immunohistochemical Study. Turkish Journal of Pathology 2017; 33 (3) 211-222. doi: 10.5146/tjpath.2017.01398

Liu S, Gonen M, Stadler ZK, Weiser MR, Hechtman JF, Vakiani E, et al. Cellular localization of PD-L1 expression in mismatch-repair deficient and proficient colorectal carcinomas. Modern Pathol. 2018; 32; 110–121. doi https://doi.org/ 10.1038 /s41379-018-0114-7.

Gottlieb CE, Mills MA, Cross VJ, Ring LK . Tumor-associated macrophage expression of PD-L1 in implants of high grade serous ovarian carcinoma: A comparison of matched primary and metastatic tumors. Gynecol. Oncol 2016 144(3) 607-612. doi http://dx.doi.org/10.1016/j.ygyno.2016.12.021

Thiem A, Hesbacher S, Kneitz H, di Primio T, Heppt MV, Hermanns HM, et al. IFN-gamma-induced PD-L1 expression in melanoma depends on p53 expression. J. Exp. Clin. Cancer Res. 2019: 38(1) 397-415 doi:10.1186/s13046-019-1403-9

Hou Y, Nitta H, Wei L, Banks MP, Lustberg M, Wesolowski R, et al. PD-L1 expression and CD8-positive T cells are associated with favorable survival in HER2-positive invasive breast cancer. Breast J. 2018; 0:911–919. Doi: 10.1111/ tbj. 13112

Bae SB, Cho HD, Oh MH, Lee JH, Jang SH, Hong SA, et al. Expression of Programmed Death Receptor Ligand 1 with High Tumour Infiltrating Lymphocytes is Associated with Better Prognosis in Breast Cancer. J Breast Cancer 2016 19(3) 242-251. doi: 10.4048/jbc.2016.19.3.242

Prognosis. In: The Merriam-Webster.com Dictionary (Internet) Merriam-Webster Inc. (cited 14-01-2010) Available from https://www.merriam-webster.com/dictionary/prognosis

Lei YY, Huang J, Zhao Q , Jiang N, Xu H , Wang Z et al. The clinicopathological parameters and prognostic significance of HER2 expression in gastric cancer patients: a meta-analysis of literature. World J Surg Oncol. 2017 15 (68). Doi 10.1186 /s12957 -017-1132-5

Fitzgibbons PL, David LP, Weaver D, Thor AD, Allred C, Clark GM, et al. Prognostic factors in breast cancer. Arch Pathol Lab Med 2000; 124 (7): 966-978

Bhurgri Y, Bhurgri A, Hassan SH, Zaidi SH, Rahim A, Sankaranarayanan R et al. Cancer Incidence in Karachi, Pakistan: First Results from Karachi Cancer Registry. Int. J. Cancer 2000 : 85, 325–329

Soysal SD, Tzankov A, Muenst SE. Role of the Tumor Microenvironment in Breast Cancer. Pathobiology 2015; 82(3-4):142-52. doi:10.1159/000430499.

Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, Von PJ, et al. Atezolizumab versus docetaxel in patients with previously treated nonsmall-cell lung cancer (OAK): a phase 3, openlabel, multicentre randomised controlled trial. Lancet 2016;387:1837.

Duncan DJ, Scott M, Scorer P, Barker C. Assessment of PD-L1 mRNA and protein expression in non-small cell lung cancer, head and neck squamous cell carcinoma and urothelial carcinoma tissue specimens using RNAScope and immunohistochemistry. PloS One. 2019 14(4): e 0215393 1-12 doi: 10.1371/journal.pone.0215393

Nagato T, Ohkuri T, Ohara K, Hirata Y, Kishibe K, Komabayashi Y, et al. Programmed death-ligand 1 and its soluble form are highly expressed in nasal natural killer/T-cell lymphoma: a potential rationale for immunotherapy. Cancer Immunol Immunother 2017;66:877–90

Zhou J, Mahoney KM, Giobbie-Hurder A, Zhao F, Lee S, Liao X, et al. Soluble PD-L1 as a Biomarker in Malignant Melanoma Treated with Checkpoint Blockade. Cancer Immunol Res. 2017;5(6):480-492. doi: 10.1158/2326-6066

Theodoraki MN, Yerneni S, Hoffmann TK, Gooding WE, Whiteside TL. Clinical significance of PD-L1+ exosomes in plasma of head and neck cancer patients. Clin Cancer Res. 2018; 24:896–905

Soliman H, Khalil F, Antonia S. PD-L1 Expression is Increased in a subset of Basal Type Breast Cancer Cells. PLOS One 2014 9(2) e 88575 https://doi.org/10.1371/ journal.pone. 0088557

Gatalica Z, Snyder C, Maney T, Ghazalpour A, Holterman D, Xiao N et al. Programmed Cell Death 1 (PD-1) and Its Ligand (PD-L1) in Common Cancers and Their Correlation with Molecular Cancer Type. Cancer Epidemiol Biomarkers 2014; 23(12): 2965-2970. doi: 10.1158/1055-9965

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 J Cancer. 2016;7(7):784–793 doi:10.7150/jca.14549

Yuan J, Zhang J, Zhu Y, Li N, Tian T, Li Y, et al. Programmed death-ligand-1 expression in advanced gastric cancer detected with RNA in situ hybridization and its clinical significance. Oncotarget 2016. 7:39671-39679

Okuma Y, Hosomi Y, Nakahara Y, Watanabe K, Sagawa Y, Homma S. High plasma levels of soluble programmed cell death ligand 1 are prognostic for reduced survival in advanced lung cancer. Lung Cancer 2017;104:1-6. Doi 10.1016/j. lungcan.2016.11.023

Uhercik M, Sanders AJ, Owen S, Davies EL, Sharma AK, Jiang WG, et al. Clinical Significance of PD1 and PDL1 in Human Breast Cancer. Anticancer Res. 2017;37(8):4249-54

Pinato DJ, Shiner RJ, White SD, Black JR, Trivedi P, Stebbing J, et al. Intra-tumoral heterogeneity in the expression of programmed-death (PD) ligands in isogeneic primary and metastatic lung cancer: Implications for immunotherapy. Oncoimmunology 2016.;5(9) 1213934 1-7

Patel SP, Kurzrock R. PD-L1 expression as a predictive biomarker in cancer immunotherapy. Mol Cancer Ther 2015;14:847–56

Kwa MJ, Adams S. Checkpoint inhibitors in triple-negative breast cancer (TNBC): Where to go from here. ACS Journals Cancer 2018; 124 (10): 2086-2103

NCI dictionary of cancer terms- National Cancer Institute.(Internet) (cited 16-01-2020.) Available from https://www.cancer.gov/publications/dictionaries/cancer-terms

Botti G, Collina F, Scognamiglio G, Rao F, Peluso V, DeCecio R, et al. Programmed death ligand 1 (PD-L1) tumor expression is associated with a better prognosis and diabetic disease in triple negative breast cancer patients. Int. J. Mol. Sci. 2017; 18(2): 459- 469. https://doi.org/10.3390/ijms18020459

Beckers RK, Selinger CI, Vilain R, Madore J, Wilmott JS, Harvey K, et al. Programmed death ligand 1 expression in triple-negative breast cancer is associated with tumour-infiltrating lymphocytes and improved outcome. Histopathology 2016; 69: 25–34. DOI: 10.1111/his.12904

Wang ZQ, Milne K, Derocher H, Webb JR, Nelson BH, Watson PH. PD-L1 and intratumoral immune response in breast cancer. Oncotarget 2017; 8: 51641-51651.

Baptista MZ, Sarian LO, Derchain SF, Pinto GA, Vassallo J. Prognostic significance of PD-L1 and PD-L2 in breast cancer. Human Pathology 2015;47(1): 78-84. http://dx.doi.org/ 10.1016/j.humpath.2015.09.006.

Sabatier R, Finetti P, Mamessier E, Adelaide J, Chaffanet M, Ali H, et al. Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget 2015 6(7), 5449–5464

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

Qin T, Zeng YD, Qin, G, Xu F, Lu JB, Fang WF, et al. High PD-L1 expression was associated with poor prognosis in 870 Chinese patients with breast cancer. Oncotarget 2015; 6(32): 33972–33981. doi:10.18632/oncotarget.5583

Zhang M, Sun H, Zhao S, Wang Y, Pu H, Wang Y, et al. Expression of PD-L1 and prognosis in breast cancer: a meta-analysis. Oncotarget 2017;8(19):31347-31354.

Mori H, Kubo M, Yamaguchi R, Nishimura R, Osako T, Arima N et al. The combination of PD-L1 expression and decreased tumor-infiltrating lymphocytes is associated with a poor prognosis in triple-negative breast cancer. Oncotarget 2017;8(9):15584-15592.

Cruz LM, Czerniecki BJ. Immunotherapy for Breast Cancer is Finally at the Doorstep: Immunotherapy in Breast Cancer. Ann Surg Oncol 2018; 25(10):2852-2857

Planes GL, Rochigneux P, Bertucci F, Chrétien AS, Viens P, Sabatier R, et al. PD-1/PD-L1 Targeting in Breast Cancer: The First Clinical Evidences Are Emerging. A Literature Review. Cancers (Basel) 2019; 11(7):1033-1058.

Iwai Y, Hamanishi J, Chamoto K, Honjo T. Cancer immunotherapies targeting the PD-1 signaling pathway. J Biomed Sci. 2017; 24(1):26-37. doi: 10.1186/s12929-017-0329-9

Schmid P, Park Y, Muñoz-Couselo C, Kim SB, Sohn J, Im SA, et al. Pembrolizumab plus chemotherapy as neoadjuvant treatment of high- risk, early- stage triple -negative breast cancer: results from the Phase 1b open- label multicohort KEYNOTE 173 study. Ann Oncology 2020; 31(5): 569-581

Downloads

Published

2021-01-01

How to Cite

Kazmi, S. ., Shawana, S. ., & Jamal, N. . (2021). PD-L1 in Breast Cancers and its Prognostic Significance. Journal of Bahria University Medical and Dental College, 11(1), 40–43. https://doi.org/10.51985/AUSB2062

Issue

Section

Review Article

Most read articles by the same author(s)