The breast cancer immune microenvironment is modified by neoadjuvant chemotherapy

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Claudia Urueña
Paola Lasso
David Bernal-Estevez
Diego Rubio
Ana Janeth Salazar
Mercedes Olaya
Alfonso Barreto
Mauricio Tawil
Lilian Torregrosa
Susana Fiorentino
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[1] Pontificia Universidad Javeriana,Grupo de Inmunobiología y Biología Celular, Unidad de Investigación en Ciencias Biomédicas, Facultad de Ciencias
[2] Fundación Salud de los Andes,Grupo de Investigación en Inmunología y Oncología Clínica
[3] Hospital Universitario San Ignacio,Departamento de Patología
[4] Pontificia Universidad Javeriana,Departamento de Cirugía y Especialidades, Hospital Universitario San Ignacio, Centro Javeriano de Oncología, Facultad de Medicina
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Neoadjuvant chemotherapy (NAT) in breast cancer (BC) has been used to reduce tumor burden prior to surgery. However, the impact on prognosis depends on the establishment of Pathological Complete Response (pCR), which is influenced by tumor-infiltrating lymphocyte levels and the activation of the antitumor immune response. Nonetheless, NAT can affect immune infiltration and the quality of the response. Here, we showed that NAT induces dynamic changes in the tumor microenvironment (TME). After NAT, an increase of regulatory T cells and a decrease of CD8+ T cells was found in tumor, correlated with the presence of metastatic cells in lymph nodes. In addition, an increase of polymorphonuclear myeloid-derived suppressor like cells was found in luminal patients post-NAT. pCR patients showed a balance between the immune populations, while non-pCR patients presented an inverse relationship in the frequency of CD68+ versus CD3+, CD8+, and CD20+ cells. Moreover, activated T cells were found in peripheral blood, as well as an increase in T cell clonality with a lower diversity post-NAT. Overall, these results shown that NAT induces an activation of immune response, however, a balance in the TME seems to be related to a better antigenic presentation and therefore a better response to treatment.
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