Comprehensive proteome profiling of imunne cells in breast cancer patients

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Cytotoxic lymphocytes are mediators of cell-mediated immune defence and play a crucial role in tumor surveillance. In this study, we employed label-free quantitative proteomics using nano-UHPLC coupled with Orbitrap mass spectrometry to analyze CD8+ T lymphocytes isolated from peripheral blood of patients with benign breast lesions and different breast cancer (BC) subtypes - luminal A, luminal B, and triple-negative breast cancer (TNBC) - in comparison with healthy controls.
Our results identified subtype-specific alterations in proteins involved in cytotoxicity, cytolysis, and RNA metabolism. We observed consistent downregulation of key cytotoxic effectors such as granzymes (GZMA, GZMH, GZMM) and perforin 1 (PRF1) in benign and luminal B patients. In contrast, GZMK was significantly upregulated in TNBC. Furthermore, gene set enrichment analysis revealed robust downregulation of the RNA degradation pathway across all patient groups, with decreased expression of Sm-like proteins (LSM2, LSM3, LSM5), suggesting a potential mechanism for regulating gene expression during T cell activation.
These findings indicate that peripheral blood-derived CD8+ T cells exhibit distinct proteomic profiles that reflect different immunological responses in benign breast conditions as well as in breast cancer subtypes including Luminal A, Luminal B, and triple-negative breast cancer. Our study highlights the potential of peripheral CD8+ T cell proteomics as a minimally invasive biomarker source for monitoring immune dysregulation in breast cancer and provides insights into the systemic immune alterations associated with disease progression.

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