Department of Medical Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
Cancer Medicine, Jikei University Graduate School of Medicine, Tokyo, Japan.
Breast Cancer Res Treat. 2023 Jan;197(2):287-297. doi: 10.1007/s10549-022-06787-x. Epub 2022 Nov 16.
Stromal tumor-infiltrating lymphocytes (TILs) are independent prognostic factors in systemically untreated early-stage triple-negative breast cancer (TNBC). Other immune biomarkers including CD8, CD20, programmed cell death-ligand 1 (PD-L1), and tertiary lymphoid structures (TLS) are also reported to be associated with prognosis. However, whether combining other immune biomarkers with TILs would allow for further prognostic stratification is unknown.
We retrospectively analyzed 125 patients with early-stage TNBC not receiving perioperative chemotherapy. Stromal TILs and TLS were evaluated on hematoxylin-eosin slides. PD-L1 expression was evaluated using the SP142 assay. CD8 and CD20 were assessed by immunohistochemistry and counted by digital pathology.
Immune biomarker levels were positively correlated (p < 0.001). Adding CD8 and PD-L1 to multivariable analysis including clinicopathological factors (stage and histological grade) and TILs significantly improved the prognostic model (likelihood ratio χ = 9.24, p = 0.01). In Cox regression analysis, high CD8 was significantly associated with better prognosis [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.48-0.98, p = 0.04], and PD-L1 positivity was significantly associated with worse prognosis (HR 4.33, 95%CI 1.57-11.99, p = 0.005). Patients with high CD8/PD-L1 (-) tumors had the most favorable prognosis [5 year invasive disease-free survival (iDFS), 100%], while patients with low CD8/PD-L1( +) tumors had the worst prognosis (5 year iDFS, 33.3%).
CD8 and PD-L1 levels add prognostic information beyond TILs for early-stage TNBC not receiving perioperative chemotherapy. CD8-positive T cells and PD-L1 may be useful for prognostic stratification and in designing future clinical trials of TNBC.
在未经系统治疗的早期三阴性乳腺癌（TNBC）患者中，肿瘤浸润性淋巴细胞（TILs）是独立的预后因素。其他免疫生物标志物，包括 CD8、CD20、程序性细胞死亡配体 1（PD-L1）和三级淋巴结构（TLS），也被报道与预后相关。然而，是否将其他免疫生物标志物与 TILs 相结合可以进行进一步的预后分层尚不清楚。
我们回顾性分析了 125 例未接受围手术期化疗的早期 TNBC 患者。在苏木精-伊红切片上评估间质 TIL 和 TLS。使用 SP142 检测评估 PD-L1 表达。通过免疫组化评估 CD8 和 CD20，并通过数字病理学进行计数。
免疫生物标志物水平呈正相关（p<0.001）。在包括临床病理因素（分期和组织学分级）和 TILs 的多变量分析中加入 CD8 和 PD-L1 显著改善了预后模型（似然比 χ=9.24，p=0.01）。在 Cox 回归分析中，高 CD8 与更好的预后显著相关[风险比（HR）0.69，95%置信区间（CI）0.48-0.98，p=0.04]，PD-L1 阳性与更差的预后显著相关（HR 4.33，95%CI 1.57-11.99，p=0.005）。高 CD8/PD-L1（-）肿瘤患者的预后最佳[5 年无侵袭性疾病生存率（iDFS）为 100%]，而低 CD8/PD-L1（+）肿瘤患者的预后最差（5 年 iDFS 为 33.3%）。
CD8 和 PD-L1 水平为未接受围手术期化疗的早期 TNBC 提供了 TILs 以外的预后信息。CD8 阳性 T 细胞和 PD-L1 可能有助于预后分层，并为 TNBC 的未来临床试验设计提供依据。
