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PD-1/PD-L1 expression in a series of intracranial germinoma and its association with Foxp3+ and CD8+ infiltrating lymphocytes.

PD-1/PD-L1 expression in a series of intracranial germinoma and its association with Foxp3+ and CD8+ infiltrating lymphocytes.
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Liu B, Arakawa Y, Yokogawa R, Tokunaga S, Terada Y, Murata D, Matsui Y, Fujimoto KI, Fukui N, Tanji M, Mineharu Y, Minamiguchi S, Miyamoto S,


Liu B, Arakawa Y, Yokogawa R, Tokunaga S, Terada Y, Murata D, Matsui Y, Fujimoto KI, Fukui N, Tanji M, Mineharu Y, Minamiguchi S, Miyamoto S, (click to view)

Liu B, Arakawa Y, Yokogawa R, Tokunaga S, Terada Y, Murata D, Matsui Y, Fujimoto KI, Fukui N, Tanji M, Mineharu Y, Minamiguchi S, Miyamoto S,

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PloS one 2018 04 0413(4) e0194594 doi 10.1371/journal.pone.0194594

Abstract

One histopathological characteristic of intracranial germinoma is abundant tumor-infiltrating lymphocytes (TILs) showing a two-cell pattern with large undifferentiated tumor cells. The programmed cell death 1 (PD-1)/programmed cell death 1 ligand (PD-L) axis has recently been recognized as an anti-tumor immune system. To evaluate intratumor immune status in intracranial germinoma, we examined expressions of PD-1 and PD-L1 (clone 28-8) and subtypes of TILs. Expressions of PD-1 and PD-L1 were detected immunohistochemically in 25 formalin-fixed, paraffin-embedded tumor specimens from 24 patients with intracranial germinoma consisting of 22 primary and 3 recurrent tumors. To evaluate subtypes of TILs, quantification of lymphocytes with CD3, CD8, CD4, and Foxp3 was performed. Statistical analyses were performed among PD-1, PD-L1 and subtypes of TILs. In 25 tumor tissue, expressions of PD-1 in TILs and PD-L1 in tumor cells were identified in 96% (24/25) and 92% (23/25), respectively. Expression of PD-1 was associated with CD3+ TIL density. Expression of PD-1 correlated with Foxp3+ TIL density and CD8+ TIL density, but not with CD4+ TIL density. Furthermore, expression of PD-1 correlated strongly with Foxp3+/CD4+ ratio. Taken together, increase of PD-1+ expression is associated with accumulation of Foxp3+ and CD8+ TILs. These findings intimate that PD-1/PD-L1 axis might shape the immune infiltration suggesting a modulation of the immune response and subsequent tumor growth in intracranial germinoma. Anti-PD-1 and anti-PD-L1 are potential immune therapeutic strategies in intracranial germinoma.

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