Tumor-Infiltrating Cd4+ T Lymphocytes in Early Breast Cancer Reflect Lymph Node Involvement

Abstract

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.

Leukocyte composition of human breast cancer

“…High FoxP3 counts correlate with reduced overall and relapse-free survival in estrogen receptor (ER)-positive tumors (43), and pCR to neoadjuvant CTX is associated with reduced FoxP3 grading (44,45). Although two studies examining T-cell infiltration by flow cytometry found conflicting results regarding the CD8:CD4 ratio and lymph node metastasis (46,47), the number of CD8 + T cells within tissue has been associated with improved patient survival (48). We have also reported a CD68/ CD4/CD8 immune signature predicting overall and relapse-free survival, with inverse correlations evident for CD4 when used in conjunction with other markers (6).…”

Breastfeeding and its Relationship with Reduction of Breast Cancer: A Review

“…Although components of the immune system are present, many breast tumours progressively grow and spread; therefore, the role of tumour-infiltrating leukocytes in the tumour microenvironment is unclear (Marsigliante et al, 1999). The association of tumour-infiltrating CD4+ T lymphocytes with lymph node metastases suggests a role for these cells in the spread of tumour cells to the lymph nodes in patients with early breast cancer (Macchetti et al, 2006).…”

Increased frequency of nonconventional double positive CD4CD8 αβ T cells in human breast pleural effusions

“…Most studies on breast cancer concurred to establish a predominance of T cells and a paucity of B cells and NK cells among tumor associated lymphocytes (TAL). [2][3][4][5][6][7] However, further characterization of these T cells in term of phenotype, specificity and function remains to be addressed and a possible correlation between TAL amounts or quality and breast cancer prognosis. 2 During the last decade, several nonconventional T-cell subsets were discovered on the basis of their function and/or phenotype.…”