Peripheral Blood CD8+ T-Lymphocyte Immune Response in Benign and Subpopulations of Breast Cancer Patients

Author:

Lenárt Marek1,Bober Peter2ORCID,Marcin Miroslav2ORCID,Tkáčiková Soňa2ORCID,Kacírová Mária3,Alexovič Michal2,Tóth Dávid4,Madárová Natália1,Radoňak Jozef1,Urdzík Peter4ORCID,Fedačko Ján3ORCID,Sabo Ján2

Affiliation:

1. 1st Department of Surgery, Faculty of Medicine, University of Pavol Jozef Šafárik and UNLP in Košice, Trieda SNP 1, 04011 Košice, Slovakia

2. Department of Medical and Clinical Biophysics, Faculty of Medicine, University of Pavol Jozef Šafárik in Košice, Trieda SNP 1, 04011 Košice, Slovakia

3. Center of Clinical and Preclinical Research MEDIPARK, Faculty of Medicine, University of Pavol Jozef Šafárik in Košice, Trieda SNP 1, 04011 Košice, Slovakia

4. Department of Gynaecology and Obstetrics, Faculty of Medicine, University of Pavol Jozef Šafárik and UNLP in Košice, Trieda SNP 1, 04011 Košice, Slovakia

Abstract

Peripheral blood CD8+ T lymphocytes play a crucial role in cell-mediated immunity and tumor-related immune responses in breast cancer. In this study, label-free quantification analysis and gene set enrichment analysis (GSEA) of CD8+ T lymphocytes in the peripheral blood of benign patients and patients with different breast cancer (BC) subtypes, i.e., luminal A, luminal B, and triple-negative breast cancer (TNBC), were performed using nano-UHPLC and Orbitrap mass spectrometry. Differential protein expression in CD8+ T lymphocytes revealed significant downregulation (log2 FC ≥ 0.38 or ≤−0.38, adj. p < 0.05), particularly in proteins involved in cytotoxicity, cytolysis, and proteolysis, such as granzymes (GZMs) and perforin 1 (PRF1). This downregulation was observed in the benign group (GZMH, GZMM, and PRF1) and luminal B (GZMA, GZMH) subtypes, whereas granzyme K (GZMK) was upregulated in TNBC in comparison to healthy controls. The RNA degradation pathway was significantly downregulated (p < 0.05, normalized enrichment score (NES) from −1.47 to −1.80) across all BC subtypes, suggesting a potential mechanism for regulating gene expression during T cell activation. Also, the Sm-like proteins (LSM2, LSM3, and LSM5) were significantly downregulated in the RNA degradation pathway. Proteomic analysis of CD8+ T lymphocytes in peripheral blood across different breast cancer subtypes provides a comprehensive view of the molecular mechanisms of the systemic immune response that can significantly contribute to advancements in the diagnosis, treatment, and prognosis of this disease.

Funder

Slovak Research and Development Agency

Publisher

MDPI AG

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