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

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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.

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Acknowledgements

This study was supported by the program: “Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT) de la Dirección General de Asuntos del Personal Académico (DGAPA)” from the National Autonomous University of Mexico (UNAM). Project numbers IA204515/RA204515 and IA208717. Diana Reyes Hernandez and Alvaro Diaz Rodriguez were fellows of the project PAPIIT IA204515/RA204515. We thank Santiago Cristobal Sigrist Flores, Karen Guadalupe Garcia Castillo, Maria Fernanda Diaz Quiroz, Alejandro Gallardo Flores and Estanislao Antonio Calixto for the technical assistant.

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Authors and Affiliations

  1. Hospital de Gineco Obstetricia No. 3 del Centro Médico Nacional la Raza del Instituto Mexicano del Seguro Social, Ciudad de México, México

    Luis Alberto Solis-Castillo & Victor Hugo Villafana-Vazquez

  2. Unidad de morfología y función (UMF), Facultad de Estudios Superiores Iztacala de la Universidad Nacional Autónoma de México, Ave. De los Barrios No. 1., 54090, Tlalnepantla, Estado de México, México

    Gina Stella Garcia-Romo, Alvaro Diaz-Rodriguez, Diana Reyes-Hernandez, Elizabeth Tellez-Rivera, Jose Rafael Jimenez-Flores & Alexander Pedroza-Gonzalez

  3. Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala de la Universidad Nacional Autónoma de México, Estado de México, México

    Gina Stella Garcia-Romo, Adolfo Rene Mendez-Cruz, Jose Rafael Jimenez-Flores & Alexander Pedroza-Gonzalez

  4. Unidad de investigación en Biomedicina (UBIMED), Facultad de Estudios Superiores Iztacala de la Universidad Nacional Autónoma de México, Estado de México, México

    Alexander Pedroza-Gonzalez

  5. Laboratorios Nacionales de Servicios Experimentales (LANSE), Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Ciudad de México, México

    Victor Hugo Rosales-Garcia

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  1. Luis Alberto Solis-Castillo
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Correspondence to Alexander Pedroza-Gonzalez.

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Solis-Castillo, L.A., Garcia-Romo, G.S., Diaz-Rodriguez, A. et al. Tumor-infiltrating regulatory T cells, CD8/Treg ratio, and cancer stem cells are correlated with lymph node metastasis in patients with early breast cancer. Breast Cancer 27, 837–849 (2020). https://doi.org/10.1007/s12282-020-01079-y

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