Faculty of Medicine, UQ Centre for Clinical Research, The University of Queensland, Herston, Brisbane, QLD, Australia.
QIMR Berghofer Medical Research Institute, Herston, Brisbane, QLD, Australia.
Br J Cancer. 2020 Nov;123(11):1665-1672. doi: 10.1038/s41416-020-01065-3. Epub 2020 Sep 17.
BACKGROUND: Metaplastic breast carcinoma encompasses a heterogeneous group of tumours with differentiation into squamous and/or spindle, chondroid, osseous or rhabdoid mesenchymal-looking elements. Emerging immunotherapies targeting Programmed Death Ligand 1 (PD-L1) and immune-suppressing T cells (Tregs) may benefit metaplastic breast cancer patients, which are typically chemo-resistant and do not express hormone therapy targets. METHODS: We evaluated the immunohistochemical expression of PD-L1 and FOXP3, and the extent of tumour infiltrating lymphocytes (TILs) in a large cohort of metaplastic breast cancers, with survival data. RESULTS: Metaplastic breast cancers were significantly enriched for PD-L1 positive tumour cells, compared to triple-negative ductal breast cancers (P < 0.0001), while there was no significant difference in PD-L1 positive TILs. Metaplastic breast cancers were also significantly enriched for TILs expressing FOXP3, with FOXP3 positive intra-tumoural TILs (iTILs) associated with an adverse prognostic outcome (P = 0.0226). Multivariate analysis identified FOXP3 iTILs expression status as an important independent prognostic factor for patient survival. CONCLUSIONS: Our findings indicate the clinical significance and prognostic value of FOXP3, PD-1/PD-L1 checkpoint and TILs in metaplastic breast cancer and confirm that a subset of metaplastics may benefit from immune-based therapies.
背景: 化生性乳腺癌包含一组具有分化为鳞状和/或梭形、软骨样、骨样或横纹肌样间充质样成分的异质性肿瘤。新兴的免疫疗法靶向程序性死亡配体 1(PD-L1)和免疫抑制性 T 细胞(Tregs)可能使化生性乳腺癌患者受益,这些患者通常对化疗耐药,并且不表达激素治疗靶点。 方法: 我们评估了 PD-L1 和 FOXP3 的免疫组化表达以及肿瘤浸润淋巴细胞(TILs)的程度,这些化生性乳腺癌患者具有生存数据。 结果: 与三阴性导管乳腺癌相比,化生性乳腺癌中 PD-L1 阳性肿瘤细胞明显更丰富(P<0.0001),而 PD-L1 阳性 TILs 则没有显著差异。化生性乳腺癌中 TILs 表达 FOXP3 的比例也明显更高,FOXP3 阳性肿瘤内 TILs(iTILs)与不良预后相关(P=0.0226)。多变量分析确定 FOXP3 iTILs 表达状态是患者生存的重要独立预后因素。 结论: 我们的研究结果表明,FOXP3、PD-1/PD-L1 检查点和 TILs 在化生性乳腺癌中的临床意义和预后价值,并证实了一部分化生性乳腺癌可能受益于免疫治疗。
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