PD-1 and PD-L1 Expression in Indian Women with Breast Cancer

Kishan R Bharadwa; Kuheli Dasgupta; Suma Mysore Narayana; C Ramachandra; Suresh M C Babu; Annapoorni Rangarajan; Rekha V Kumar

doi:10.4274/ejbh.galenos.2021.2021-5-2

PD-1 and PD-L1 Expression in Indian Women with Breast Cancer

Eur J Breast Health. 2021 Dec 30;18(1):21-29. doi: 10.4274/ejbh.galenos.2021.2021-5-2. eCollection 2022 Jan.

Authors

Kishan R Bharadwa¹, Kuheli Dasgupta², Suma Mysore Narayana³, C Ramachandra⁴, Suresh M C Babu⁵, Annapoorni Rangarajan², Rekha V Kumar³

Affiliations

¹ IISc Mathematics Initiative, Indian Institute of Science (IISc), Bangalore, India.
² Department of Molecular Reproduction Development and Genetics, Indian Institute of Science (IISc), Bangalore, India.
³ Department of Pathology, Kidwai Memorial Institute of Oncology (KMIO), Bangalore, India.
⁴ Department of Surgical Oncology, Kidwai Memorial Institute of Oncology (KMIO), Bangalore, India.
⁵ Department of Medical Oncology, Kidwai Memorial Institute of Oncology (KMIO), Bangalore, India.

Abstract

Objective: The interaction between programmed cell death protein 1 (PD-1) on activated T-lymphocytes and programmed death-ligand 1 (PD-L1) on tumor cells or antigen-presenting cells sends immunosuppressive signals leading to the escape of tumor cells from the host anti-tumor immune response. Inhibiting this interaction with antibodies against PD-1 or PD-L1 is emerging as a valuable therapeutic strategy. However, tissue distribution patterns for PD-L1 and PD-1 in breast cancer patients from India are not reported, yet many clinical trials are underway. In this study the expression of PD-1 and PD-L1 in breast cancer patient samples from India was characterized.

Materials and methods: The study included 392 cases of operated breast cancer (2012-2017) from a tertiary cancer care center in Bangalore, Karnataka, India. Paraffin blocks were retrievable and receptor status was known. Immunohistochemistry (IHC) was performed using anti-PD-L1 and anti-PD-1 antibodies. RNA was isolated from 76 fresh tumors and nine adjacent normal tissues (2019). PD-L1 transcript levels were measured by RT-qPCR using Hypoxanthine-guanine phosphoribosyl transferase (HPRT) as a reference gene.

Results: Based on IHC, PD-1 expression within tumor-infiltrating immune cells (TIICs) was observed in 55/385 cases (14%) across all breast cancer types. In triple-negative breast cancer (TNBC), 21/132 cases (16%) showed PD-1 staining in TIICs. The overall expression of PD-L1 in breast tumor cells across all breast cancer subtypes and TIICs was 11% (41/378) and 39% (151/385), respectively. A relatively higher proportion of TNBC cases had PD-L1 expression in tumor cells (17/132 cases, 13%) and immune cells (68/132 cases, 52%). We also detected PD-L1 transcript expression by qRT-PCR in freshly isolated tumor samples.

Conclusion: These findings show that around 52% (68/132) of the TNBC cases express PD-L1 in TIICs. Hence, anti-PD-1/PD-L1 therapy alone or combined with chemotherapy may be a promising treatment for TNBC in Indian patients.

Keywords: Triple-negative breast cancer; immunohistochemistry; programmed cell death protein 1 (PD-1); programmed death-ligand 1 (PD-L1).