Tumor-infiltrating regulatory T cells, CD8/Treg ratio, and cancer stem cells are correlated with lymph node metastasis in patients with early breast cancer.

Abstract

BACKGROUND:

Tumor-infiltrating lymphocytes are an important component of the tumor microenvironment (TME) in breast cancer. They have been linked with tumor pathogenesis in advanced stages. However, little is known about their contribution in early phases. In this study, we analyzed the infiltration of leukocytes and cancer stem cells (CSC) in tumors from patients with early breast cancer.

METHODS:

Samples of blood and tumor tissue from 30 patients with breast cancer were collected, and the number of dendritic cells (DC), T cells, and CSC were analyzed by flow cytometry.

RESULTS:

Tumor-infiltrating CD4 and CD8 T cells expressed higher levels of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) compared with peripheral T cells. Regulatory T cells (Treg) were enriched in tumors and overexpressed glucocorticoid-induced TNFR-related protein and CTLA-4. Tumor Treg had a positive correlation with the amount of myeloid DC (mDC) and disease progression. The CD8/Treg ratio was associated with lymph node metastasis and tumor stages. The main subset of DC in early breast tumors was mDC, while plasmacytoid DC were almost absent. CSC were present in most tumors with higher frequencies in patients with lymph node metastasis. CSC were also associated with the amount of tumor-infiltrating Treg.

CONCLUSION:

Early breast cancer has an inflammatory milieu characterized by mDC, Treg, and CSC infiltration. The frequencies of Treg, CSC and CD8/Treg ratio were associated with disease progression. The composition of leukocytes and the presence of CSC in early breast tumors should be considered for the development of new therapeutic approaches.

• Authors: Luis Alberto Solis-Castillo, Gina Stella Garcia-Romo, Alvaro Diaz-Rodriguez, Diana Reyes-Hernandez, Elizabeth Tellez-Rivera, Victor Hugo Rosales-Garcia, Adolfo Rene Mendez-Cruz, Jose Rafael Jimenez-Flores, Victor Hugo Villafana-Vazquez, Alexander Pedroza-Gonzalez
• Journal: Breast cancer (Tokyo, Japan) (Breast Cancer) Vol. 27 Issue 5 Pg. 837-849 (Sep 2020) ISSN: 1880-4233 [Electronic] Japan
• PMID: 32180141 (Publication Type: Journal Article, Observational Study)

Topics

• Adult
• Aged
• Aged, 80 and over
• Breast (immunology, pathology)
• Breast Neoplasms (blood, diagnosis, immunology, pathology)
• CD4-CD8 Ratio
• CD8-Positive T-Lymphocytes (immunology)
• Dendritic Cells (immunology)
• Female
• Humans
• Lymph Nodes (immunology, pathology)
• Lymphatic Metastasis (immunology)
• Lymphocytes, Tumor-Infiltrating
• Middle Aged
• Neoplasm Grading
• Neoplastic Stem Cells (immunology)
• T-Lymphocytes, Regulatory (immunology)
• Tumor Microenvironment (immunology)