Expression of PD-1 and PD-L1 in Endometrial Cancer: Molecular and Clinical Significance

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Oct 28

PMID 37894913

Authors

Mohd Nazzary Mamat Yusof

Kah Teik Chew

Nirmala Chandralega Kampan

Mohamad Nasir Shafiee

Affiliations

Soon will be listed here.

Abstract

The landscape of diagnosing and treating endometrial cancer is undergoing a profound transformation due to the integration of molecular analysis and innovative therapeutic approaches. For several decades, the cornerstone treatments for endometrial cancer have included surgical resection, cytotoxic chemotherapy, hormonal therapy, and radiation therapy. However, in recent years, the concept of personalised medicine has gained momentum, reshaping the way clinicians approach cancer treatment. Tailoring treatments based on specific biomarkers has evolved into a standard practice in both initial and recurrent therapy protocols. This review aims to provide an in-depth exploration of the current state of molecular analysis and treatment strategies in the context of endometrial cancer, focusing on the immunological aspect of the PD-1/PD-L1 axis. Furthermore, it seeks to shed light on emerging and innovative approaches that hold promise for the future modulation of endometrial cancer treatments. In essence, as researchers delve into the complex molecular landscape of endometrial cancer and harness the understanding of the PD-1/PD-L1 axis, we are paving the way for more targeted, effective, and personalised therapies that have the potential to significantly improve the outcomes and quality of life for patients with this challenging disease.

Citing Articles

Gene expression and soluble protein level of PD-1 and its ligands (PD-L1 and PD-L2) in endometrial cancer.

Mamat Yusof M, Chew K, Kampan N, Hafizz A, Shafiee M PLoS One. 2025; 20(3):e0312765.

PMID: 40043041 PMC: 11882069. DOI: 10.1371/journal.pone.0312765.

Insulin-like Growth Factor 1 (IGF1) and Its Isoforms: Insights into the Mechanisms of Endometrial Cancer.

Hafizz A, Mohd Mokthar N, Md Zin R, Mongan N, Mamat Yusof M, Kampan N Cancers (Basel). 2025; 17(1.

PMID: 39796756 PMC: 11720045. DOI: 10.3390/cancers17010129.

A machine learning-based immune response signature to facilitate prognosis prediction in patients with endometrial cancer.

Wang X, Guan J, Feng L, Li Q, Zhao L, Li Y Sci Rep. 2024; 14(1):30801.

PMID: 39730507 PMC: 11680691. DOI: 10.1038/s41598-024-81040-7.

The role of ncRNAs and exosomes in the development and progression of endometrial cancer.

Niebora J, Wozniak S, Domagala D, Data K, Farzaneh M, Zehtabi M Front Oncol. 2024; 14:1418005.

PMID: 39188680 PMC: 11345653. DOI: 10.3389/fonc.2024.1418005.

The PD-1/PD-L1 Gateway: Peripheral Immune Regulation in the Pathogenesis of Endometriosis.

Sobstyl M, Mertowska P, Mertowski S, Zaborek-Lyczba M, Dudzinski D, Polak G Int J Mol Sci. 2024; 25(12).

PMID: 38928479 PMC: 11203925. DOI: 10.3390/ijms25126775.

References

Chen S, Zhang Z, Zheng X, Tao H, Zhang S, Ma J . Response Efficacy of PD-1 and PD-L1 Inhibitors in Clinical Trials: A Systematic Review and Meta-Analysis. Front Oncol. 2021; 11:562315. PMC: 8085334. DOI: 10.3389/fonc.2021.562315. View

Zhang S, Minaguchi T, Xu C, Qi N, Itagaki H, Shikama A . PD-L1 and CD4 are independent prognostic factors for overall survival in endometrial carcinomas. BMC Cancer. 2020; 20(1):127. PMC: 7027009. DOI: 10.1186/s12885-020-6545-9. View

Thomas S, Hussein Y, Bandyopadhyay S, Cote M, Hassan O, Abdulfatah E . Interobserver Variability in the Diagnosis of Uterine High-Grade Endometrioid Carcinoma. Arch Pathol Lab Med. 2016; 140(8):836-43. PMC: 5656271. DOI: 10.5858/arpa.2015-0220-OA. View

Talhouk A, Derocher H, Schmidt P, Leung S, Milne K, Gilks C . Molecular Subtype Not Immune Response Drives Outcomes in Endometrial Carcinoma. Clin Cancer Res. 2018; 25(8):2537-2548. DOI: 10.1158/1078-0432.CCR-18-3241. View

Schreiber R, Old L, Smyth M . Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011; 331(6024):1565-70. DOI: 10.1126/science.1203486. View

Aguirre-Ghiso J . Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer. 2007; 7(11):834-46. PMC: 2519109. DOI: 10.1038/nrc2256. View

Luchini C, Bibeau F, Ligtenberg M, Singh N, Nottegar A, Bosse T . ESMO recommendations on microsatellite instability testing for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach. Ann Oncol. 2019; 30(8):1232-1243. DOI: 10.1093/annonc/mdz116. View

Koebel C, Vermi W, Swann J, Zerafa N, Rodig S, Old L . Adaptive immunity maintains occult cancer in an equilibrium state. Nature. 2007; 450(7171):903-7. DOI: 10.1038/nature06309. View

Konstantinopoulos P, Luo W, Liu J, Gulhan D, Krasner C, Ishizuka J . Phase II Study of Avelumab in Patients With Mismatch Repair Deficient and Mismatch Repair Proficient Recurrent/Persistent Endometrial Cancer. J Clin Oncol. 2019; 37(30):2786-2794. PMC: 9798913. DOI: 10.1200/JCO.19.01021. View

10.

Shen X, Zhang L, Li J, Li Y, Wang Y, Xu Z . Recent Findings in the Regulation of Programmed Death Ligand 1 Expression. Front Immunol. 2019; 10:1337. PMC: 6587331. DOI: 10.3389/fimmu.2019.01337. View

11.

Momeni-Boroujeni A, Nguyen B, Vanderbilt C, Ladanyi M, Abu-Rustum N, Aghajanian C . Genomic landscape of endometrial carcinomas of no specific molecular profile. Mod Pathol. 2022; 35(9):1269-1278. PMC: 9427676. DOI: 10.1038/s41379-022-01066-y. View

12.

Linsley P, Greene J, Brady W, Bajorath J, Ledbetter J, Peach R . Human B7-1 (CD80) and B7-2 (CD86) bind with similar avidities but distinct kinetics to CD28 and CTLA-4 receptors. Immunity. 1994; 1(9):793-801. DOI: 10.1016/s1074-7613(94)80021-9. View

13.

Jubel J, Barbati Z, Burger C, Wirtz D, Schildberg F . The Role of PD-1 in Acute and Chronic Infection. Front Immunol. 2020; 11:487. PMC: 7105608. DOI: 10.3389/fimmu.2020.00487. View

14.

Rossi E, Schinzari G, Maiorano B, Indellicati G, Di Stefani A, Pagliara M . Efficacy of immune checkpoint inhibitors in different types of melanoma. Hum Vaccin Immunother. 2020; 17(1):4-13. PMC: 7872095. DOI: 10.1080/21645515.2020.1771986. View

15.

de Boer S, Wortman B, Bosse T, Powell M, Singh N, Hollema H . Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer. Ann Oncol. 2017; 29(2):424-430. PMC: 5834053. DOI: 10.1093/annonc/mdx753. View

16.

Dunn G, Bruce A, Ikeda H, Old L, Schreiber R . Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002; 3(11):991-8. DOI: 10.1038/ni1102-991. View

17.

Abiko K, Matsumura N, Hamanishi J, Horikawa N, Murakami R, Yamaguchi K . IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer. Br J Cancer. 2015; 112(9):1501-9. PMC: 4453666. DOI: 10.1038/bjc.2015.101. View

18.

Hussein Y, Broaddus R, Weigelt B, Levine D, Soslow R . The Genomic Heterogeneity of FIGO Grade 3 Endometrioid Carcinoma Impacts Diagnostic Accuracy and Reproducibility. Int J Gynecol Pathol. 2015; 35(1):16-24. PMC: 4934379. DOI: 10.1097/PGP.0000000000000212. View

19.

Palucka K, Banchereau J, Mellman I . Designing vaccines based on biology of human dendritic cell subsets. Immunity. 2010; 33(4):464-78. PMC: 2975953. DOI: 10.1016/j.immuni.2010.10.007. View

20.

Bregar A, Deshpande A, Grange C, Zi T, Stall J, Hirsch H . Characterization of immune regulatory molecules B7-H4 and PD-L1 in low and high grade endometrial tumors. Gynecol Oncol. 2017; 145(3):446-452. DOI: 10.1016/j.ygyno.2017.03.006. View