Type 2 diabetes alters local T-cell immune status in breast carcinoma

Abstract

Background. Breast cancer and type 2 diabetes mellitus (T2DM) are prevalent chronic diseases that substantially affect health. T2DM can remodel the tumor microenvironment (TME) through several mechanisms. Yet the influence of T2DM on T-cell infiltration in breast carcinoma remains undocumented in current literature. Objective(s). To compare the expression of ER, PR, CD4+, and CD8+ markers in invasive breast carcinoma from patients with and without T2DM, aiming to identify metabolic-driven changes in tumor biology. Materials and methods. Seventy-two women with breast carcinoma of no special type were allocated to two cohorts: 29 with T2DM and 43 without. Immunohistochemistry (Dako Autostainer Link 48) detected ER (IR657), PR (M3569), CD4 (IR649) and CD8 (GA62362-2). SPSS 23.0 analyses included Student t-, Mann-Whitney and Spearman tests for comparative evaluation. Results. Mean age and Nottingham score did not differ between cohorts (p = 0.23). Fasting glucose was higher in T2DM cases (9.9 ± 3.1 mmol/L) than in controls (5.04 ± 1.10; p = 0.001). Diabetic tumors were larger (2.9 ± 2.2 cm vs 2.10 ± 0.80; p = 0.046) and carried fewer intratumoral T-cells: CD4+ 7.8 ± 5.5 vs 10.4 ± 9.6 and CD8+ 15.2 ± 11.3 vs 17.5 ± 13.4 (p = 0.01). ER and PR positivity rates were similar between groups. In the diabetic subgroup, PR inversely correlated with Ki67 (rs = −0.49, p = 0.007), while CD4+ density correlated negatively with ER (rs = −0.32, p = 0.04), suggesting metabolic imbalance modulates hormone-immune crosstalk. Conclusion(s). T2DM does not alter ER or PR expression in NST breast carcinomas but is linked to larger tumor size and diminished intratumoral CD4+ and CD8+ lymphocyte densities. These findings indicate that metabolic dysregulation shapes the breast cancer TME and could inform tailored management.