Distinct Activation and Functional Features of CD307c+ T Lymphocytes in Peripheral Blood as Diagnostic and Prognostic Markers in Breast Cancer.

Abstract

This study aims to investigate the expression and role of CD307c in the breast cancer (BC) microenvironment, T lymphocytes of peripheral blood, particularly in BC patients at various stages, and assess its potential as a clinical diagnostic biomarker. Bioinformatics analysis was performed to investigate CD307c expression. As experimental validation, a total of 54 BC patients and 44 healthy controls (HCs) were enrolled. Flow cytometry was used to analyse CD307c expression in CD4⁺ and CD8⁺ T cells, alongside markers of T cell activation and function, such as PD-1, Ki-67, CD25, CD62L, GZMB and GZMK. Ex vivo T cell stimulation with anti-CD3 and anti-CD28 was performed to assess CD307c expression after activation. Statistical analyses, including receiver operating characteristic (ROC) curve analysis, were used to evaluate the diagnostic value of CD307c⁺ T cell subsets. Bioinformatics analysis revealed that CD307c was significantly upregulated in BC tissues compared to adjacent normal tissues, and that CD307c was mainly expressed in lymphocytes, such as B cells, T_regs, CD8⁺ T cells and NKs in the tumour microenvironment. In peripheral blood, CD307c expression was significantly higher in CD4⁺ T cells compared to CD8⁺ T cells. CD307c⁺ T cells exhibited elevated levels of Ki-67, PD-1, CD25 and CD62L, indicating increased activation and potential for immune exhaustion. Additionally, CD307c⁺ CD8⁺ T cells showed higher expression of granzyme B (GZMB) and granzyme K (GZMK), markers of cytotoxicity. In BC patients, CD307c expression was significantly higher in both CD4⁺ and CD8⁺ T cells compared to HCs, and the proportion of CD307c⁺ cells varied across cancer stages. CD307c expression in T lymphocytes is elevated in early-stage BC. CD307c⁺ T cells show enhanced activation, suggesting its potential role as a useful biomarker for early BC diagnosis and a potential therapeutic target.