Reduced Neoantigen Expression Revealed by Longitudinal Multiomics as a Possible Immune Evasion Mechanism in Glioma
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- Takahide Nejo
- 1Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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- Hirokazu Matsushita
- 2Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo, Japan.
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- Takahiro Karasaki
- 2Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo, Japan.
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- Masashi Nomura
- 1Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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- Kuniaki Saito
- 5Department of Neurosurgery, Kyorin University Faculty of Medicine, Tokyo, Japan.
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- Shota Tanaka
- 1Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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- Shunsaku Takayanagi
- 1Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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- Taijun Hana
- 1Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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- Satoshi Takahashi
- 1Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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- Yosuke Kitagawa
- 1Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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- Tsukasa Koike
- 1Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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- Yukari Kobayashi
- 2Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo, Japan.
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- Genta Nagae
- 4Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan.
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- Shogo Yamamoto
- 4Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan.
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- Hiroki Ueda
- 4Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan.
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- Kenji Tatsuno
- 4Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan.
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- Yoshitaka Narita
- 6Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan.
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- Motoo Nagane
- 5Department of Neurosurgery, Kyorin University Faculty of Medicine, Tokyo, Japan.
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- Keisuke Ueki
- 7Department of Neurosurgery, Dokkyo Medical University, Tochigi, Japan.
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- Ryo Nishikawa
- 8Department of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan.
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- Hiroyuki Aburatani
- 4Genome Science Division, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan.
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- Akitake Mukasa
- 1Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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- Nobuhito Saito
- 1Department of Neurosurgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
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- Kazuhiro Kakimi
- 2Department of Immunotherapeutics, The University of Tokyo Hospital, Tokyo, Japan.
説明
<jats:title>Abstract</jats:title> <jats:p>Immune-based therapies have shown limited efficacy in glioma thus far. This might be at least in part due to insufficient numbers of neoantigens, thought to be targets of immune attack. In addition, we hypothesized that dynamic genetic and epigenetic tumor evolution in gliomas might also affect the mutation/neoantigen landscape and contribute to treatment resistance through immune evasion. Here, we investigated changes in the neoantigen landscape and immunologic features during glioma progression using exome and RNA-seq of paired primary and recurrent tumor samples obtained from 25 WHO grade II–IV glioma patients (glioblastoma, IDH-wild-type, n = 8; grade II–III astrocytoma, IDH-mutant, n = 9; and grade II–III oligodendroglioma, IDH-mutant, 1p/19q-codeleted, n = 8). The number of missense mutations, predicted neoantigens, or expressed neoantigens was not significantly different between primary and recurrent tumors. However, we found that in individual patients the ratio of expressed neoantigens to predicted neoantigens, designated the “neoantigen expression ratio,” decreased significantly at recurrence (P = 0.003). This phenomenon was particularly pronounced for “high-affinity,” “clonal,” and “passenger gene–derived” neoantigens. Gene expression and IHC analyses suggested that the decreased neoantigen expression ratio was associated with intact antigen presentation machinery, increased tumor-infiltrating immune cells, and ongoing immune responses. Our findings imply that decreased expression of highly immunogenic neoantigens, possibly due to persistent immune selection pressure, might be one of the immune evasion mechanisms along with tumor clonal evolution in some gliomas.</jats:p>
収録刊行物
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- Cancer Immunology Research
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Cancer Immunology Research 7 (7), 1148-1161, 2019-07-01
American Association for Cancer Research (AACR)
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詳細情報 詳細情報について
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- CRID
- 1360285711354162560
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- ISSN
- 23266074
- 23266066
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- データソース種別
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