免疫检查点抑制剂的治疗候选物由三阴性乳腺癌（TNBC）中肿瘤浸润淋巴细胞（TILs）和程序性死亡配体 1（PD-L1）表达的状态所阐明。
The therapeutic candidate for immune checkpoint inhibitors elucidated by the status of tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression in triple negative breast cancer (TNBC).
机构信息
Department of Breast Surgery, National Hospital Organization (NHO) Hokkaido Cancer Center, 4-2 Kikusui, Shiroishi-ku, Sapporo, 003-0804, Japan.
Department of Clinical Pathology, National Hospital Organization (NHO) Hokkaido Cancer Center, 4-2 Kikusui, Shiroishi-ku, Sapporo, 003-0804, Japan.
出版信息
Breast Cancer. 2018 Jan;25(1):34-42. doi: 10.1007/s12282-017-0781-0. Epub 2017 May 9.
BACKGROUND
The status of tumor-infiltrating lymphocytes (TILs) is a prognostic factor for triple negative breast cancer (TNBC). Recent studies have shown that programmed cell death 1 (PD-1) or programmed death ligand 1 (PD-L1) is expressed on T lymphocytes or tumor cells modulating antitumor immunity. The regulation of immune checkpoints between tumor cells and T lymphocytes may serve as a target for improvement of TNBC prognosis. We investigated TILs and PD-L1 status in TNBCs before or after preoperative systemic therapy (PST) to elucidate the clinical significance of PD-L1 expression.
METHODS
Ninety patients received PST, and materials of core needle biopsies (CNB) taken before PST were available for 32 patients. TILs were scored as "% stromal", and tumors were defined as High-TILs (≥30%) or Low-TILs (<30%). The expression of PD-L1 was assessed by immunohistochemistry.
RESULTS
TILs status in CNB is significant in pathological therapeutic grade: 1 vs. 2 or 3 (p = 0.0359). Disease-free survival (DFS) in patients with Low-TIL tumors were significantly worse than those with High-TIL tumors (p = 0.0383), but overall survival (OS) showed no significance (p = 0.0772). However, in patients with Low-TIL tumors, both DFS and OS in patients with High-PD-L1 expression were extremely unfavorable than in patients with Low-PD-L1 expression (p = 0.0032, p = 0.0002).
CONCLUSION
The patients with TNBCs with combined Low-TILs and High-PD-L1 status in pre-PST situation showed unfavorable prognosis. The subset of TNBCs with Low-TILs and High-PD-L1 status could be the therapeutic target for immune checkpoint inhibitor.
背景
肿瘤浸润淋巴细胞（TILs）的状态是三阴性乳腺癌（TNBC）的预后因素。最近的研究表明，程序性细胞死亡 1（PD-1）或程序性死亡配体 1（PD-L1）在调节抗肿瘤免疫的 T 淋巴细胞或肿瘤细胞上表达。肿瘤细胞与 T 淋巴细胞之间免疫检查点的调节可能成为改善 TNBC 预后的靶点。我们研究了 TNBC 患者在术前全身治疗（PST）前后的 TILs 和 PD-L1 状态，以阐明 PD-L1 表达的临床意义。
方法
90 例患者接受了 PST，其中 32 例患者的 PST 前核心针活检（CNB）材料可用。TILs 评分按“%间质”评分，肿瘤分为高 TILs（≥30%）或低 TILs（<30%）。PD-L1 的表达通过免疫组化评估。
结果
CNB 中的 TILs 状态在病理治疗分级中具有显著意义：1 级与 2 级或 3 级（p=0.0359）。低 TIL 肿瘤患者的无病生存率（DFS）明显差于高 TIL 肿瘤患者（p=0.0383），但总生存率（OS）无显著差异（p=0.0772）。然而，在低 TIL 肿瘤患者中，高 PD-L1 表达患者的 DFS 和 OS 均明显差于低 PD-L1 表达患者（p=0.0032，p=0.0002）。
结论
在 PST 前，同时存在低 TILs 和高 PD-L1 状态的 TNBC 患者预后不良。低 TILs 和高 PD-L1 状态的 TNBC 亚组可能是免疫检查点抑制剂的治疗靶点。
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