Expression of immune checkpoints (PD-L1 and IDO) and tumour-infiltrating lymphocytes in breast cancer

Noura Alkhayyal; Noha M Elemam; Amal Hussein; Sulaman Magdub; Majd Jundi; Azzam A Maghazachi; Iman M Talaat; Riyad Bendardaf

doi:10.1016/j.heliyon.2022.e10482

Expression of immune checkpoints (PD-L1 and IDO) and tumour-infiltrating lymphocytes in breast cancer

Heliyon. 2022 Aug 30;8(9):e10482. doi: 10.1016/j.heliyon.2022.e10482. eCollection 2022 Sep.

Authors

Noura Alkhayyal^{1

2

3}, Noha M Elemam^{1

2}, Amal Hussein⁴, Sulaman Magdub⁵, Majd Jundi³, Azzam A Maghazachi^{1

2}, Iman M Talaat^{1

2}, Riyad Bendardaf^{1

3}

Affiliations

¹ Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
² Sharjah Institute of Medical Research, University of Sharjah, Sharjah, United Arab Emirates.
³ University Hospital Sharjah, Sharjah, United Arab Emirates.
⁴ Department of Basic Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
⁵ Department of Pathology, Tawam Hospital, Alain, United Arab Emirates.

Abstract

Background: Breast cancer (BC) has become the most common cancer globally in 2020 as well as in the United Arab Emirates. The breast tumor microenvironment is composed of various immune cell types, including lymphocytes. Tumour-infiltrating lymphocytes (TILs) play a crucial role in tumor eradication and progression. Further, immune checkpoint markers such as programmed death receptor ligand 1 (PD-L1) and indoleamine-2,3-dioxygenase (IDO) have been associated with tumor evasion from the immune system. In this study, we aimed to explore the status of TILs, PD-L1 and IDO as well as to investigate their association with the clinicopathological parameters.

Materials and methods: A total of 59 patients diagnosed with primary infiltrating BC were selected, after which tissue sections were stained to identify TILs along with immunohistochemical staining of PD-L1 and IDO. Moreover, in-silico tools were used to assess the expression of PD-L1, IDO and CD3ε in various molecular subtypes of BC.

Results: It was found that the percentage of TILs correlated with estrogen receptor (ER) and progesterone receptor (PR) expression. This was supported by the finding that most of the triple-negative breast cancer (TNBC) cases belonged to the group with a high percentage of TILs (h-TILs). Similarly, the expression of PD-L1 and IDO was correlated with the ER and PR, whereas TNBC cases showed a high expression of PD-L1 and IDO. This goes in line with the in-silico findings where the TNBC group showed the highest expression of PD-L1 and IDO as well as the T cell marker CD3ε.

Conclusion: This study highlighted a possible link between the immunosuppressive markers PD-L1 and IDO with TILs density in the BC microenvironment.

Keywords: Breast cancer; IDO; Immune checkpoints; PD-L1; TILs.