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

Autor: Lenárt, Marek, Bober, Peter, Marcin, Miroslav, Tkáčiková, Soňa, Kacírová, Mária, Alexovič, Michal, Tóth, Dávid, Madárová, Natália, Radoňak, Jozef, Urdzík, Peter, Fedačko, Ján, Sabo, Ján
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Zdroj: International Journal of Molecular Sciences; Jun2024, Vol. 25 Issue 12, p6423, 16p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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