CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
不同乳腺癌新辅助治疗后肿瘤免疫微环境表型的比较
英文原题：Comparison of the tumor immune microenvironment phenotypes in different breast cancers after neoadjuvant therapy.
查看英文原题
Comparison of the tumor immune microenvironment phenotypes in different breast cancers after neoadjuvant therapy.
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中文摘要
新辅助治疗（NAT）用于治疗早期乳腺癌，尤其是三阴性乳腺癌（TNBC）。NAT 可提高不同乳腺癌患者的病理完全缓解（pCR）率。近年来，靶向程序性死亡 1（PD-1）或程序性死亡配体 1（PD-L1）的免疫检查点抑制剂联合 NAT 在早期乳腺癌患者中显示出抗肿瘤活性。
然而，不同亚型乳腺癌（如 TNBC、激素受体阳性（HR+）和人表皮生长因子受体 2 扩增（HER2+））的肿瘤免疫微环境（TME）及其在 NAT 后的变化仍有待充分表征。
我们分析了接受 NAT 后手术的 TNBC（n = 27）、HR+（n = 24）和 HER2+（n = 30）乳腺癌患者的 NAT 前肿瘤活检标本。通过基于免疫荧光的微环境分析鉴定了TIL（肿瘤浸润淋巴细胞）（TILs）的不同免疫标志物（PD-1、PD-L1、CD3 和 CD8）。分别计数癌实质内 TILs（iTILs）和癌间质内 TILs（sTILs）。
我们发现，TNBC 患者肿瘤和间质中的 PD-L1+ 细胞显著高于其他患者。在所有亚型中，pCR 患者的 PD-L1+ sTILs 显著高于非 pCR 患者。TNBC 患者中 B 细胞记忆、活化 CD4+ 记忆 T 细胞、滤泡辅助性 T 细胞以及 M0 和 M1 巨噬细胞的浸润评分相对较高，表明 TNBC 具有免疫反应性 TME。TCGA-BRCA RNA-seq 分析表明，与 HR+ 和 HER2+ 患者相比，PD-L1 在 TNBC 患者中高表达。TNBC 患者中较高的 PD-L1 表达与显著更长的总生存期（OS）相关。
我们的结果表明，在乳腺癌中，TNBC 的 iTILs 和 sTILs 的 PD-L1 表达水平最高。与 HR+ 和 HER2+ 患者相比，TNBC 患者具有显著不同的免疫反应性 TME，提示这些患者可能从免疫治疗中获得有利结局。
此外，PD-L1+ 可能是 TNBC 患者接受 NAT 后 pCR 的有力预测因子。
展开英文摘要原文
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.
论文信息
- 作者
- Han M、Li J、Wu S、Wu C、Yu Y、Liu Y
- 单位
- Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.China
- 期刊
- Cancer medicine2023 Feb
- 原文标识
- PubMed 36073303 · DOI 10.1002/cam4.5207
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