Department of Oncology, University Hospital of North Norway, Tromso, Norway. Institute of Clinical Medicine, The Arctic University of Norway, Tromso, Norway.
Institute of Clinical Medicine, The Arctic University of Norway, Tromso, Norway.
Clin Cancer Res. 2015 Jun 1;21(11):2635-43. doi: 10.1158/1078-0432.CCR-14-1905. Epub 2015 Feb 13.
Immunoscore is a prognostic tool defined to quantify in situ immune cell infiltrates, which appears to be superior to the tumor-node-metastasis (TNM) classification in colorectal cancer. In non-small cell lung cancer (NSCLC), no immunoscore has been established, but in situ tumor immunology is recognized as highly important. We have previously evaluated the prognostic impact of several immunological markers in NSCLC, yielding the density of stromal CD8(+) tumor-infiltrating lymphocytes (TIL) as the most promising candidate. Hence, we validate the impact of stromal CD8(+) TIL density as an immunoscore in NSCLC.
The prognostic impact of stromal CD8(+) TILs was evaluated in four different cohorts from Norway and Denmark consisting of 797 stage I-IIIA NSCLC patients. The Tromso cohort (n = 155) was used as training set, and the results were further validated in the cohorts from Bodo (n = 169), Oslo (n = 295), and Denmark (n = 178). Tissue microarrays and clinical routine CD8 staining were used for all cohorts.
Stromal CD8(+) TIL density was an independent prognostic factor in the total material (n = 797) regardless of the endpoint: disease-free survival (P < 0.001), disease-specific survival (P < 0.001), or overall survival (P < 0.001). Subgroup analyses revealed significant prognostic impact of stromal CD8(+) TIL density within each pathologic stage (pStage). In multivariate analysis, stromal CD8(+) TIL density and pStage were independent prognostic variables.
Stromal CD8(+) TIL density has independent prognostic impact in resected NSCLC, adds prognostic impact within each pStage, and is a good candidate marker for establishing a TNM-Immunoscore.
免疫评分是一种用于量化原位免疫细胞浸润的预后工具，它在结直肠癌中的表现似乎优于肿瘤-淋巴结-转移（TNM）分类。在非小细胞肺癌（NSCLC）中，尚未建立免疫评分，但原位肿瘤免疫学被认为非常重要。我们之前评估了 NSCLC 中几种免疫标志物的预后影响，结果表明基质 CD8+肿瘤浸润淋巴细胞（TIL）的密度是最有前途的候选标志物。因此，我们验证了基质 CD8+TIL 密度作为 NSCLC 免疫评分的影响。
评估了来自挪威和丹麦的四个不同队列的 797 例 I-IIIA 期 NSCLC 患者中基质 CD8+TIL 的预后影响。特罗姆瑟队列（n=155）用作训练集，结果在博多（n=169）、奥斯陆（n=295）和丹麦（n=178）队列中进一步验证。所有队列均使用组织微阵列和临床常规 CD8 染色。
无论终点是无病生存期（P<0.001）、疾病特异性生存期（P<0.001）还是总生存期（P<0.001），基质 CD8+TIL 密度都是总材料（n=797）的独立预后因素。亚组分析显示，在每个病理分期（pStage）内，基质 CD8+TIL 密度均具有显著的预后影响。在多变量分析中，基质 CD8+TIL 密度和 pStage 是独立的预后变量。
基质 CD8+TIL 密度在可切除 NSCLC 中具有独立的预后影响，在每个 pStage 内增加了预后影响，是建立 TNM-免疫评分的候选标志物。
