Immunotyping of tumor‑infiltrating lymphocytes in triple‑negative breast cancer and genetic characterization

Gomez‑Μacias,Gabriela Sofia; Molinar‑Flores,Guillermo; Lopez‑Garcia,Carlos A.; Santuario‑Facio,Sandra; Decanini‑Arcaute,Horacio; Valero‑Elizondo,Javier; Treviño‑Alvarado,Victor; Ortiz‑Lopez,Rocio; Dono,Antonio; Esteban‑Zubero,Eduardo; Alatorre‑Jimenez,Moises A.; Garza,Cynthia Villarreal; Peña‑Curiel,Omar; Cardona‑Huerta,Servando

doi:10.3892/ol.2020.12000

Immunotyping of tumor‑infiltrating lymphocytes in triple‑negative breast cancer and genetic characterization

Authors:
- Gabriela Sofia Gomez‑Μacias
- Guillermo Molinar‑Flores
- Carlos A. Lopez‑Garcia
- Sandra Santuario‑Facio
- Horacio Decanini‑Arcaute
- Javier Valero‑Elizondo
- Victor Treviño‑Alvarado
- Rocio Ortiz‑Lopez
- Antonio Dono
- Eduardo Esteban‑Zubero
- Moises A. Alatorre‑Jimenez
- Cynthia Villarreal Garza
- Omar Peña‑Curiel
- Servando Cardona‑Huerta
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Affiliations: Department of Pathology, Hospital San José TecSalud, Tecnológico de Monterrey, Monterrey, Nuevo León 64710, México, Laboratorio de Investigacion, Tecnologico de Monterrey, Monterrey, Nuevo León 64710, México, Department of Pathology, Hospital Christus Muguerza of Alta Especialidad, Monterrey, Nuevo León 64060, México, Breast Cancer Center, Hospital San José, TecSalud, Tecnológico de Monterrey, Monterrey, Nuevo León 64710, México, Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center at Houston, Medical School, Houston, TX 77030, USA, Department of Emergencies, San Pedro Hospital, Logroño, La Rioja 26006, Spain, Department of Pediatrics, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA
Published online on: August 20, 2020 https://doi.org/10.3892/ol.2020.12000
Article Number: 140
Copyright: © Gomez‑Μacias et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tumor‑infiltrating lymphocytes (TILs) reflect the host immune response against cancer cells. Immunomodulators have been recently suggested as a novel therapeutic strategy against triple‑negative breast cancer (TNBC). However, the TIL profile in TNBC has not been thoroughly investigated. In the present study, the percentage, immunophenotype and genetic profiles of TILs in pre‑surgical tumor samples of patients with TNBC were evaluated prior to neoadjuvant chemotherapy (NAC). Patients diagnosed with breast cancer at Hospital San José TecSalud were consecutively and prospectively enrolled in the present study between August 2011 and August 2015. The pathological response to NAC was evaluated using the de Miller‑Payne and MD Anderson Cancer Center system. TIL percentage (low, intermediate, and high) was evaluated using special hematoxylin‑eosin staining on the core needle biopsies. The immunophenotype of TILs was assessed by immunohistochemistry (IHC) for CD3+, CD4+ and CD8+. In addition, the gene expression profile of CD3, CD4, CD8, CD20, CD45, forkhead box P3, interleukin 6, programmed cell death 1 and CD274 molecule was assessed in all patients. A total of 26 samples from patients with TNBC prior to NAC were included in the present study. TILs were low in 30.7%, intermediate in 38.4% and elevated in 30.7% of tumors. CD3+ and CD4+ counts were associated with the pathological response to NAC (P=0.04). Finally, an overexpression pattern of CD3, CD4, CD8, CD45 and CD20 genes was observed in patients with a partial or complete pathological response. The present results demonstrated that TILs may predict the pathological response to NAC in patients with TNBC. Furthermore, a more accurate association was identified between the high expression levels of CD3, CD4, CD8, CD45 and CD20 genes and partial and complete pathological response, compared with the association between high expression and IHC alone.

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