Immune microenvironment changes induced by neoadjuvant chemotherapy in triple-negative breast cancers: the MIMOSA-1 study.
Breast Cancer Res
; 23(1): 61, 2021 05 26.
Article
em En
| MEDLINE
| ID: mdl-34039396
ABSTRACT
BACKGROUND:
The immune microenvironment (IME) of triple-negative breast cancers (TNBCs) and its modulation by neoadjuvant chemotherapy (NACT) remain to be fully characterized. Our current study aims to evaluate NACT-induced IME changes and assess the prognostic value of specific immune biomarkers.METHODS:
Tumor-infiltrating lymphocytes (TILs) were identified from hematoxylin-eosin-stained sections of paired pre- and post-NACT tumor samples from a TNBC cohort (n = 66) and expression of PD-L1, TIM-3, and LAG-3 evaluated by immunohistochemistry.RESULTS:
Overall TIL counts and PD-L1 expression did not differ pre- and post-NACT, but there was a response-specific statistically significant difference. TIL counts decreased in 65.5% of patients who achieved a pathological complete response (pCR) and increased in 56.8% of no-pCR patients (p = 0.0092). PD-L1 expression was significantly more frequently lost after NACT in pCR than in no-pCR patients (41.4% vs 16.2%, p = 0.0020). TIM-3 positivity (≥ 1%) was significantly more frequent after NACT (p < 0.0001) with increases in expression levels occurring more frequently in no-pCR than in pCR patients (51.4% vs 31%). LAG-3 expression significantly decreased after NACT, but there was no difference between response groups. Before NACT, a high TIL count (> 10%) was significantly associated with better overall survival (OS), p = 0.0112. After NACT, PD-L1 positivity and strong TIM-3 positivity (≥ 5%) were both associated with significantly worse OS (p = 0.0055 and p = 0.0274, respectively). Patients positive for both PD-L1 and TIM-3 had the worst prognosis (p = 0.0020), even when only considering patients who failed to achieve a pCR, p = 0.0479.CONCLUSIONS:
NACT induces significant IME changes in TNBCs. PD-L1 and TIM-3 expression post-NACT may yield important prognostic information for TNBC patients.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Terapia Neoadjuvante
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Microambiente Tumoral
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Neoplasias de Mama Triplo Negativas
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article