1] Department of Pathology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea [2] Department of Pathology, Kyungpook National University School of Medicine, 680 Gukchaebosang-ro, Jung-gu, Daegu 700-842, Korea.
Br J Cancer. 2013 Nov 12;109(10):2705-13. doi: 10.1038/bjc.2013.634. Epub 2013 Oct 15.
Tumour-infiltrating lymphocytes (TILs) are known to be associated with response to primary systemic therapy (PST) in breast cancer. This study was conducted to assess the association of TIL subsets with pathological complete response (pCR) after PST in breast cancer in relation to breast cancer subtype, breast cancer stem cell (BCSC) phenotype and epithelial-mesenchymal transition (EMT).
The pre-chemotherapeutic biopsy specimens of 153 breast cancer patients who underwent surgical resection after anthracycline- or anthracycline/taxane-based PST were analysed. TIL subsets (CD4+, CD8+, and FOXP3+ TILs), BCSC phenotype, and the expression of EMT markers were evaluated by immunohistochemistry and were correlated with pCR after PST.
Infiltration of CD4+ and CD8+ T lymphocytes was closely correlated with BCSC phenotype and EMT. High levels of CD4+, CD8+, and FOXP3+ TILs were associated with pCR, and CD8+ TILs were found to be an independent predictive factor for pCR. In addition, CD8+ TILs were associated with pCR irrespective of breast cancer subtype, CD44+/CD24- phenotype, EMT, and chemotherapeutic regimen in subgroup analyses.
These findings indicate that CD8+ cytotoxic T lymphocytes are a key component of TILs associated with chemo-response and can be used as a reliable predictor of response to anthracycline- or anthracycline/taxane-based PST in breast cancer.
浸润肿瘤的淋巴细胞(TILs)与乳腺癌的初始全身治疗(PST)反应有关。本研究旨在评估 TIL 亚群与乳腺癌亚型、乳腺癌干细胞(BCSC)表型和上皮-间充质转化(EMT)相关的 PST 后病理完全缓解(pCR)之间的关系。
分析了 153 例接受蒽环类或蒽环类/紫杉烷类 PST 后行手术切除的乳腺癌患者的化疗前活检标本。通过免疫组织化学评估 TIL 亚群(CD4+、CD8+和 FOXP3+ TILs)、BCSC 表型和 EMT 标志物的表达,并与 PST 后的 pCR 相关联。
CD4+和 CD8+淋巴细胞浸润与 BCSC 表型和 EMT 密切相关。高水平的 CD4+、CD8+和 FOXP3+ TILs与 pCR 相关,CD8+ TILs 被发现是 pCR 的独立预测因子。此外,在亚组分析中,CD8+ TILs 与 pCR 相关,而与乳腺癌亚型、CD44+/CD24-表型、EMT 和化疗方案无关。
这些发现表明 CD8+细胞毒性 T 淋巴细胞是与化疗反应相关的 TIL 的关键组成部分,可作为蒽环类或蒽环类/紫杉烷类 PST 治疗乳腺癌反应的可靠预测因子。