CLUSTER OF DIFFERENTIATION 3 ZETA-CHAIN EXPRESSION AS A POTENTIAL BIOMARKER OF IMMUNE DYSFUNCTION IN AN INDIAN BREAST CANCER COHORT: CORRELATION WITH INTERLEUKIN-6 AND INTERLEUKIN-13 LEVELS

Abstract

Objectives: This study aimed to evaluate cluster of differentiation 3 zeta (CD3ζ) expression in peripheral blood mononuclear cells (PBMC) and serum interleukin-6 (IL)-6 and IL-13 levels and to determine their association in breast cancer (BC) patients. Methods: To determine the expression of CD3ζ in 45 patients with BC patients diagnosed at any stage, without undergoing treatment, and 15 age-matched controls were included in the study. PBMCs were isolated, and flow cytometry analysis was done. Serum samples were collected from the same patients and healthy controls to check for IL-6 and IL-13 through enzyme-linked immunosorbent assay. Results: A total of 60 participants (45 BC patients and 15 healthy controls) were included. BC patients showed significantly reduced CD3ζ mean fluorescence intensity (MFI) and CD3ζ⁺ T-cell percentages compared with controls (p≤0.001), while serum IL-6 and IL-13 levels were significantly elevated (both p<0.001). CD3ζ expression remained consistently lower across all tumor stages, whereas cytokine levels generally increased with disease progression. CD3ζ MFI was negatively correlated with IL-6 (r=−0.433, p=0.001) and IL-13 (r=−0.431, p=0.001) levels and positively correlated with CD3ζ⁺ T-cell percentages (r=0.640, p<0.001). IL-6 and IL-13 levels demonstrated a strong positive correlation (r=0.779, p<0.001). Conclusion: Low CD3ζ expression along with elevated IL-6 and IL-13 levels indicates impaired T-cell function and immune evasion in BC. These findings provide insight into systemic immune dysfunction and suggest potential biomarkers for prognosis and immunotherapeutic response.