Platform of Transfer in Biology of Cancer, Georges Francois Leclerc Cancer Center, 1 Rue Du Professeur Marion, 21000 Dijon, France; GIMI Genetic and Immunology Medical Institute, 21000 Dijon, France.
Department of Medical Oncology, Georges Francois Leclerc Cancer Center, 1 Rue Du Professeur Marion, 21000 Dijon, France.
Eur J Cancer. 2019 Oct;120:97-106. doi: 10.1016/j.ejca.2019.07.020. Epub 2019 Sep 6.
Tumour-infiltrating lymphocyte (TIL) detection by histology is associated with outcomes in breast cancer; nevertheless, analysis standardisation is difficult. We determined whether transcriptomic data could generate a genomic signature that estimated TIL infiltrates and determined patient prognosis in localised breast cancer.
Using 1928 transcriptomic profiles of pure cells, we generated a genetic signature specific to lymphocyte, myeloid, stromal and cancer cells. We then computed a score based on this signature and tested the association between the score and the TILs estimated for patients in an adjuvant setting from public and private data sets. We tested the capacity of the transcriptomic RNA TIL score to predict disease-free survival (DFS) or overall survival (OS) through multivariate Cox models adjusted for classical clinical variables and PAM50 molecular classification in two public data sets (Carte d'Identité des Tumeurs [CIT], n = 530; Metabric, n = 1832).
A high RNA TIL score was significantly associated with the presence of a high level of TILs as assessed by histology. The score was also associated with DFS and OS in multivariate Cox models adjusted for molecular and clinical variables (CIT: OS hazard ratio [HR] = 0.15 [0.04, 0.61], p-value = 0.007; DFS: 0.27 [0.08, 0.8] p-value = 0.02; Metabric: OS HR = 0.87 [0.77, 0.97], p-value = 0.01). The association between the RNA TIL score and survival was tested by univariate analysis in each molecular subgroup; the RNA TIL score was associated with survival only in basal-like tumours.
Determination of the TIL rate using a transcriptomic signature is feasible and has a high prognostic value in patients with basal-like tumours in an adjuvant setting.
组织学检测肿瘤浸润淋巴细胞（TIL）与乳腺癌的预后相关；然而，分析标准化具有一定难度。本研究旨在确定转录组数据是否可以生成一种基因组特征，该特征可以估计TIL 浸润程度，并确定局部乳腺癌患者的预后。
利用 1928 个纯细胞的转录组谱，我们生成了一个专门针对淋巴细胞、髓样细胞、基质细胞和癌细胞的基因特征。然后，我们基于该特征计算一个评分，并在公共和私人数据集的辅助治疗环境中测试该评分与患者 TIL 估计值之间的关联。我们通过多变量 Cox 模型测试了转录组 RNA TIL 评分预测无病生存（DFS）或总生存（OS）的能力，该模型调整了经典临床变量和 PAM50 分子分类，两个公共数据集（Carte d'Identité des Tumeurs [CIT]，n=530；Metabric，n=1832）。
高 RNA TIL 评分与组织学评估的高水平 TIL 存在显著相关。该评分与多变量 Cox 模型调整后的分子和临床变量的 DFS 和 OS 也相关（CIT：OS 风险比[HR]为 0.15[0.04, 0.61]，p 值=0.007；DFS：0.27[0.08, 0.8]，p 值=0.02；Metabric：OS HR 为 0.87[0.77, 0.97]，p 值=0.01）。通过单变量分析在每个分子亚组中测试了 RNA TIL 评分与生存的关系；RNA TIL 评分仅与基底样肿瘤的生存相关。
在辅助治疗环境中，使用转录组特征确定 TIL 率是可行的，并且对基底样肿瘤患者具有较高的预后价值。
