Immune correlates of the differing pathological and therapeutic effects of neoadjuvant chemotherapy in breast cancer.
Eur J Surg Oncol
; 46(1): 77-84, 2020 01.
Article
em En
| MEDLINE
| ID: mdl-31563296
PURPOSE: To evaluate immune responses paralleling the pathological and therapeutic effects of neoadjuvant chemotherapy (NAC) in the tumor microenvironment of breast cancer. PATIENTS AND METHODS: 38 patients with stages II and III breast cancer received NAC followed by surgery in 2012-2018. Peripheral natural killer (pNK) cell activity, tumor-infiltrating lymphocytes (TILs), and levels of tumor microenvironmental factors were assessed before and after NAC. RESULTS: In univariate analysis, grade 2 (G2) and better therapeutic effects were significantly associated with high post-NAC levels of NK cells and interleukin-6, and tended to be associated with higher CD4, CD8 and CTLA-4 transcripts. Disappearance of axillary lymph node metastasis (Ax+) was significantly associated with 1) increased NK and pNK levels, 2) decreased vascular endothelial growth factor (VEGF) transcripts after NAC, 3) the presence of ≥5% TILs, and tended to be associated with higher CTLA-4 levels before NAC. Multivariate analysis showed that G2 and better therapeutic effects were significantly associated with higher NK levels after NAC (OR = 1.07, 95% CI 1.00-1.14; p = 0.0255), and that disappearance of Ax+ was significantly associated with the presence of ≥5% pre-NAC TILs (OR = 19.87, 95% CI 2.24-175.80; pâ¯=â¯0.0072). CONCLUSIONS: Increased NK cells after NAC, together with increased CD4+ and CD8+ T-cells, and decreased CTLA-4+ T cells and VEGF correlate with beneficial therapeutic effects. Systemic activation of pNK cell activity and the presence of pre-NAC TILs may improve the elimination of Ax + together with decreased immunosuppression by VEGF in tumors.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Quimioterapia Adjuvante
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Microambiente Tumoral
Limite:
Adult
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Aged
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Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article