Tumor-infiltrating CD4+ T Lymphocytes in Early Breast Cancer Reflect Lymph Node Involvement

Background: The role of immune system in the pathogenesis and progression of breast cancer is a subject of controversy, and this stimulated us to investigate the association of the immunophenotype of tumor-infiltrating lymphocytes in early breast cancer with the spread of tumor cells to axillary lymph nodes.

Methods: Tumor samples from 23 patients with early breast cancer from the Department of Gynecology and Obstetrics of Ribeirão Preto Medical School (USP) were obtained at the time of biopsy and submitted to an enzyme-digestion procedure for the extraction of tumor-infiltrating lymphocytes. The lymphocytes extracted were analyzed by dual-color flow cytometry with monoclonal antibodies in these combinations: CD3 FITC/CD19 PE, CD3 FITC/CD4 PE, CD3 FITC/CD8 PE, and CD16/56 PerCP, which are specific for immunophenotyping of T and B lymphocytes, helper and cytotoxic T lymphocytes, and natural killer (NK) cells. The mean percentage of these cells was used for comparing groups of patients with or without lymph node metastasis.

Results: The mean value for T-lymphocyte infiltration was 24.72 +/- 17.37%; for B-lymphocyte infiltration, 4.22 +/- 6.27%; for NK-cell infiltration, 4.41 +/- 5.22%, and for CD4(+) and CD8(+) T-lymphocyte infiltration, 12.43 +/- 10.12% and 11.30 +/- 15.09%, respectively. Only mean values of T- and CD4(+) T-lymphocyte infiltration were higher in the group of patients with lymph node metastasis, while no differences were noted in the other lymphocyte subpopulations.

Conclusion: The association of tumor-infiltrating CD4(+) T lymphocytes with lymph node metastasis suggests a role for these cells in the spread of neoplasia to lymph nodes in patients with early breast cancer.