Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Gattamelata 64, 35128, Padova, Italy.
Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Via Gattamelata 64, 35128, Padova, Italy.
Breast Cancer Res. 2018 Jun 22;20(1):62. doi: 10.1186/s13058-018-1003-1.
Tumor-infiltrating lymphocytes (TILs) evaluated in primary breast cancer (BC) convey prognostic information. Limited data in the metastatic setting are available.
Secondary lesions from 94 BC patients, 43 triple-negative (TN) and 51 HER2-positive, were evaluated for TILs and expression of CD8, FOXP3, and PD-L1 by immunohistochemistry.
TILs levels on metastasis were generally low (median 5%) and did not differ between TN and HER2+ tumors. Younger patients showed significantly lower TILs (p = 0.002). In HER2+ patients, TILs were higher in lung metastases as compared to other sites (p = 0.038). TILs composition was different across metastatic sites: skin metastases presented higher FOXP3 (p = 0.002) and lower CD8/FOXP3 ratio (p = 0.032). Patients treated for metastatic BC prior to biopsy had lower CD8 (overall: p = 0.005, HER2+: p = 0.011, TN: p = 0.075). In TN patients, median overall survival (OS) was 11.8 and 62.9 months for patients with low and high TILs, respectively (HR 0.29, 95%CI 0.11-0.76, log-rank p = 0.008). CD8/FOXP3 ratio was also prognostic in TN patients (median OS 8.0, 13.2, and 54.0 months in 1st, 2nd and 3th tertile, log-rank p = 0.019). Both TILs and CD8/FOXP3 ratio were independent factors at multivariate analysis. Counterintuitively, in HER2+ BC, low TILs tumors showed better prognosis (median OS 53.7 vs 39.9 months in TILs low and TILs high, not statistically significant).
Our findings indicate the relevance of TILs as prognostic biomarker for TNBC even in the advanced setting and provide novel hypothesis-generating data on potential sources of immune heterogeneity of metastatic BC.
浸润肿瘤的淋巴细胞（TILs）在原发性乳腺癌（BC）中的评估可提供预后信息。转移性疾病中可用的相关数据有限。
对 94 名 BC 患者的继发性病变（43 名三阴性[TN]和 51 名 HER2 阳性）进行 TILs 和 CD8、FOXP3 和 PD-L1 的免疫组化评估。
转移瘤中的 TILs 水平通常较低（中位数为 5%），并且在 TN 和 HER2+肿瘤之间没有差异。年轻患者的 TILs 明显较低（p=0.002）。在 HER2+患者中，与其他部位相比，肺转移瘤中的 TILs 更高（p=0.038）。TILs 的组成在转移部位之间不同：皮肤转移瘤的 FOXP3 更高（p=0.002），CD8/FOXP3 比值更低（p=0.032）。在活检前接受转移性 BC 治疗的患者的 CD8 水平较低（总体：p=0.005，HER2+：p=0.011，TN：p=0.075）。在 TN 患者中，低 TILs 和高 TILs 患者的总生存（OS）中位数分别为 11.8 和 62.9 个月（HR 0.29，95%CI 0.11-0.76，对数秩 p=0.008）。CD8/FOXP3 比值在 TN 患者中也是预后因素（OS 中位数分别为 1 级、2 级和 3 级的 8.0、13.2 和 54.0 个月，对数秩 p=0.019）。在多变量分析中，TILs 和 CD8/FOXP3 比值均为独立因素。反直觉的是，在 HER2+BC 中，低 TILs 肿瘤的预后更好（TILs 低和 TILs 高的 OS 中位数分别为 53.7 和 39.9 个月，无统计学意义）。
我们的研究结果表明，TILs 作为 TNBC 的预后生物标志物具有相关性，即使在晚期也具有相关性，并为转移性 BC 免疫异质性的潜在来源提供了新的假设生成数据。
