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Comparison of the tumor immune microenvironment phenotypes in different breast cancers after neoadjuvant therapy

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机构: [1]Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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关键词: immune microenvironment neoadjuvant therapy PD-L1 triple-negative breast cancer tumor-infiltrating lymphocytes

摘要:
Neoadjuvant therapy (NAT) treats early-stage breast cancers, especially triple-negative breast cancers (TNBCs). NAT improves pathological complete response (pCR) rates for different breast cancer patients. Recently, immune checkpoint inhibitors that target programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) in combination with NAT have shown antitumor activity in patients with early breast cancer. However, the tumor immune microenvironment (TME) in different subtypes of breast cancers, like TNBC, hormone receptor-positive (HR+), and human epidermal growth factor receptor 2 amplified (HER2+) and its changes by NAT remain to be fully characterized. We analyzed pre-NAT tumor biopsies from TNBC (n = 27), HR+ (n = 24), and HER2+ (n = 30) breast cancer patients who received NAT, followed by surgery. The different immune makers (PD-1, PD-L1, CD3, and CD8) of tumor-infiltrating lymphocytes (TILs) were identified with immunofluorescence-based microenvironment analysis. TILs within cancer parenchyma (iTILs) and in cancer stroma (sTILs) were counted separately. We found that PD-L1+ cells in tumor and stroma were significantly higher in TNBC patients than in others. PD-L1+ sTILs were significantly higher in pCR than in non-pCR patients of all the subtypes. The infiltration scores of B-cell memory, T-cell CD4+ memory activated, T-cell follicular helper, and Macrophage M0 and M1 were relatively higher in TNBC patients, indicating immunoreactive TME in TNBC. Analysis of TCGA-BRCA RNA-seq indicated that PD-L1 was highly expressed in TNBC patients compared with HR+ and HER2+ patients. Higher PD-L1 expression in TNBC patients was associated with significantly longer overall survival (OS). Our results demonstrated that PD-L1 expression level of iTILs and sTILs is highest in TNBC among breast cancers. TNBC patients had significantly different immunoreactive TME compared with HR+ and HER2+ patients, suggesting potentially favorable outcomes for immunotherapy in these patients. Also, PD-L1+ could be a powerful predictor of pCR in TNBC patients after NAT.

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出版当年[2023]版:
大类 | 2 区 医学
小类 | 3 区 肿瘤学
最新[2025]版:
大类 | 3 区 医学
小类 | 3 区 肿瘤学
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出版当年[2023]版:
Q2 ONCOLOGY
最新[2024]版:
Q2 ONCOLOGY

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第一作者机构: [1]Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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通讯机构: [1]Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China [*1]Department of Pathology, the Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, 050000 Shijiazhuang, China
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