Density of tumor-infiltrating lymphocytes correlates with extent of brain edema and overall survival time in patients with brain metastases
Density of tumor-infiltrating lymphocytes correlates with extent of brain edema and overall survival time in patients with brain metastases
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DOI：
10.1080/2162402x.2015.1057388
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发表时间：
2016-01-01
期刊：
影响因子：
7.2
通讯作者：
Preusser, Matthias
中科院分区：
文献类型：
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作者：
Berghoff, Anna S.;Fuchs, Elisabeth;Preusser, Matthias
脑的免疫微环境不同于其他器官，肿瘤浸润淋巴细胞（til）在脑转移（BM）中的作用是癌症最常见和最具破坏性的并发症之一，目前尚不清楚。我们研究了116例BM标本的TIL亚群及其对CD3、CD8、CD45RO、FOXP3、PD1和PD-L1的免疫组化影响。免疫评分按先前公布的方法计算。总体而言，我们在115/116例（99.1%）BM标本中发现TIL浸润。PD-L1在19/67 (28.4%)BM标本中表达明显，与TIL密度无相关性（p < 0.05）。TIL密度与皮质类固醇给药无关（p < 0.05）。不同TIL亚型浸润密度差异有统计学意义（p < 0.001）；CD3+ TILs高浸润发生率最高（95/116;81.9%），PD1+ TILs高浸润发生率最低（18/116;15.5%;p < 0.001）。TIL密度在黑色素瘤中最高，其次是肾细胞癌和肺癌BM （p < 0.001）。术前磁共振成像显示CD8(+) TILs密度与瘤周水肿程度呈正相关（p = 0.031）。CD3+ （15 vs. 6个月，p = 0.015）、CD8(+) （15 vs. 11个月，p = 0.030）和CD45RO+ TILs （18 vs. 8个月，p = 0.006）的密度与有利的中位OS时间呈正相关。免疫评分与生存预后有显著相关性（27个月vs 10个月；p < 0.001）。在多变量分析中，免疫评分对预后的影响与已建立的预后参数无关（HR 0.612, p < 0.001）。总之，我们的数据表明，密集的TILs浸润在脑脊髓瘤中很常见，并且与瘤周脑水肿的数量和生存预后相关，从而确定免疫系统是影响中枢神经系统的癌症患者的潜在生物标志物。需要进一步的研究来证实我们的发现。
The immune microenvironment of the brain differs from that of other organs and the role of tumor-infiltrating lymphocytes (TILs) in brain metastases (BM), one of the most common and devastating complication of cancer, is unclear. We investigated TIL subsets and their prognostic impact in 116 BM specimens using immunohistochemistry for CD3, CD8, CD45RO, FOXP3, PD1 and PD-L1. The Immunoscore was calculated as published previously. Overall, we found TIL infiltration in 115/116 (99.1%) BM specimens. PD-L1 expression was evident in 19/67 (28.4%) BM specimens and showed no correlation with TIL density (p > 0.05). TIL density was not associated with corticosteroid administration (p > 0.05). A significant difference in infiltration density according to TIL subtype was present (p < 0.001; Chi Square); high infiltration was most frequently observed for CD3+ TILs (95/116; 81.9%) and least frequently for PD1+ TILs (18/116; 15.5%; p < 0.001). Highest TIL density was observed in melanoma, followed by renal cell cancer and lung cancer BM (p < 0.001). The density of CD8(+) TILs correlated positively with the extent of peritumoral edema seen on pre-operative magnetic resonance imaging (p = 0.031). The density of CD3+ (15 vs. 6 mo; p = 0.015), CD8(+) (15 vs. 11 mo; p = 0.030) and CD45RO+ TILs (18 vs. 8 mo; p = 0.006) showed a positive correlation with favorable median OS times. Immunoscore showed significant correlation with survival prognosis (27 vs. 10 mo; p < 0.001). The prognostic impact of Immunoscore was independent from established prognostic parameters at multivariable analysis (HR 0.612, p < 0.001). In conclusion, our data indicate that dense TILs infiltrates are common in BM and correlate with the amount of peritumoral brain edema and survival prognosis, thus identifying the immune system as potential biomarker for cancer patients with CNS affection. Further studies are needed to substantiate our findings.