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Breast Cancer Research

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01-12-2021 | Breast Cancer | Research article

Immune microenvironment changes induced by neoadjuvant chemotherapy in triple-negative breast cancers: the MIMOSA-1 study

Authors: Victor Sarradin, Amélie Lusque, Thomas Filleron, Florence Dalenc, Camille Franchet

Published in: Breast Cancer Research | Issue 1/2021

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.

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Title: Immune microenvironment changes induced by neoadjuvant chemotherapy in triple-negative breast cancers: the MIMOSA-1 study
Authors: Victor Sarradin
Amélie Lusque
Thomas Filleron
Florence Dalenc
Camille Franchet
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Cytostatic Therapy
Published in: Breast Cancer Research / Issue 1/2021
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/s13058-021-01437-4

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Abstract

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