Density of tumor-infiltrating lymphocytes correlates with extent of brain edema and overall survival time in patients with brain metastases

作者：Anna Sophie Berghoff, Elisabeth Fuchs, Gerda Ricken, Bernhard Mlecnik, Gabriela Bindea, Thomas Spanberger, Monika Hackl, Georg Widhalm, Karin Ute Dieckmann, Daniela Prayer, Amélie M. Bilocq, Harald Heinzl, Christoph Carl Zielinski, Rupert Bartsch, Peter Birner, Jérôme Galon, Matthias Preusser · 发表于：OncoImmunology · 年份：2015 · DOI：10.1080/2162402x.2015.1057388 · 被引用次数：314 · 研究领域：Brain Metastases and Treatment、Cancer Immunotherapy and Biomarkers、Glioma Diagnosis and Treatment

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 Im...