Intratumoural immune cell landscape in germinoma reveals multipotent lineages and exhibits prognostic significance.

Brain Neoplasms / diagnosis Cell Lineage / immunology Gene Expression Profiling Germinoma / diagnosis Humans Prognosis Transcriptome Tumor Microenvironment / immunology
RNA in situ hybridization RNA sequence germ cell tumour immune checkpoint immunome tumour-infiltrating lymphocyte

Journal

Neuropathology and applied neurobiology
ISSN: 1365-2990
Titre abrégé: Neuropathol Appl Neurobiol
Pays: England
ID NLM: 7609829

Informations de publication

Date de publication:
02 2020
Historique:
received: 13 12 2018
accepted: 03 06 2019
pubmed: 11 6 2019
medline: 5 2 2021
entrez: 11 6 2019
Statut: ppublish

Résumé

Alterations in microenvironments are a hallmark of cancer, and these alterations in germinomas are of particular significance. Germinoma, the most common subtype of central nervous system germ cell tumours, often exhibits massive immune cell infiltration intermingled with tumour cells. The role of these immune cells in germinoma, however, remains unknown. We investigated the cellular constituents of immune microenvironments and their clinical impacts on prognosis in 100 germinoma cases. Patients with germinomas lower in tumour cell content (i.e. higher immune cell infiltration) had a significantly longer progression-free survival time than those with higher tumour cell contents (P = 0.03). Transcriptome analyses and RNA in-situ hybridization indicated that infiltrating immune cells comprised a wide variety of cell types, including lymphocytes and myelocyte-lineage cells. High expression of CD4 was significantly associated with good prognosis, whereas elevated nitric oxide synthase 2 was associated with poor prognosis. PD1 (PDCD1) was expressed by immune cells present in most germinomas (93.8%), and PD-L1 (CD274) expression was found in tumour cells in the majority of germinomas examined (73.5%). The collective data strongly suggest that infiltrating immune cells play an important role in predicting treatment response. Further investigation should lead to additional categorization of germinoma to safely reduce treatment intensity depending on tumour/immune cell balance and to develop possible future immunotherapies.

Identifiants

DOI: 10.1111/nan.12570 PMID: 31179566
pubmed: 31179566
doi: 10.1111/nan.12570
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

111-124

Informations de copyright

© 2019 British Neuropathological Society.

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Auteurs

H Takami (H)

Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.
Department of Neurosurgery, Faculty of Medicine, The University of Tokyo Hospital, Tokyo, Japan.
ORCID: 0000-0001-9742-7462

S Fukushima (S)

Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.

K Aoki (K)

Division of Gene and Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan.

K Satomi (K)

Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.
Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan.

K Narumi (K)

Division of Gene and Immune Medicine, National Cancer Center Research Institute, Tokyo, Japan.

N Hama (N)

Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.

Y Matsushita (Y)

Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.
Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan.

K Fukuoka (K)

Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.
Division of Pediatric Neuro-Oncology, Saitama Medical University International Medical Center, Saitama, Japan.

K Yamasaki (K)

Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.
Department of Pediatrics, Osaka City General Hospital, Osaka, Japan.

T Nakamura (T)

Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.
Department of Neurosurgery, Graduate School of Medicine, Yokohama City University, Kanagawa, Japan.
ORCID: 0000-0003-1422-8957

A Mukasa (A)

Department of Neurosurgery, Faculty of Medicine, The University of Tokyo Hospital, Tokyo, Japan.
Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

N Saito (N)

Department of Neurosurgery, Faculty of Medicine, The University of Tokyo Hospital, Tokyo, Japan.

T Suzuki (T)

Department of Neuro-Oncology/Neurosurgery, Saitama Medical University International Medical Center, Saitama, Japan.

T Yanagisawa (T)

Division of Pediatric Neuro-Oncology, Saitama Medical University International Medical Center, Saitama, Japan.

H Nakamura (H)

Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Department of Neurosurgery, Kurume University, Fukuoka, Japan.

K Sugiyama (K)

Department of Neurosurgery, Faculty of Medicine, Hiroshima University, Hiroshima, Japan.

K Tamura (K)

Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

T Maehara (T)

Department of Neurosurgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

M Nakada (M)

Department of Neurosurgery, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.

M Nonaka (M)

Department of Neurosurgery, Kansai Medical University Hospital, Osaka, Japan.

A Asai (A)

Department of Neurosurgery, Kansai Medical University Hospital, Osaka, Japan.

K Yokogami (K)

Department of Neurosurgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

H Takeshima (H)

Department of Neurosurgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.

T Iuchi (T)

Department of Neurosurgery, Chiba Cancer Center, Chiba, Japan.

Y Kanemura (Y)

Department of Neurosurgery, Osaka National Hospital, National Hospital Organization, Osaka, Japan.
Department of Biomedical Research and Innovation, Institute for Clinical Research, Osaka National Hospital, National Hospital Organization, Osaka, Japan.

K Kobayashi (K)

Department of Neurosurgery, Faculty of Medicine, Kyorin University, Tokyo, Japan.

M Nagane (M)

Department of Neurosurgery, Faculty of Medicine, Kyorin University, Tokyo, Japan.

K Kurozumi (K)

Department of Neurological Surgery, Dentistry, and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan.

K Yoshimoto (K)

Department of Neurosurgery, Kyusyu University Hospital, Fukuoka, Japan.

M Matsuda (M)

Department of Neurosurgery, University of Tsukuba Hospital, Ibaraki, Japan.

A Matsumura (A)

Department of Neurosurgery, University of Tsukuba Hospital, Ibaraki, Japan.

Y Hirose (Y)

Department of Neurosurgery, Fujita Health University Hospital, Aichi, Japan.

T Tokuyama (T)

Department of Neurosurgery, Hamamatsu University Hospital, Shizuoka, Japan.

T Kumabe (T)

Department of Neurosurgery, Kitasato University, Kanagawa, Japan.

K Ueki (K)

Department of Neurosurgery, Dokkyo Medical Univeristy, Tochigi, Japan.

Y Narita (Y)

Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan.

S Shibui (S)

Department of Neurosurgery and Neuro-Oncology, National Cancer Center Hospital, Tokyo, Japan.

Y Totoki (Y)

Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.

T Shibata (T)

Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.

Y Nakazato (Y)

Department of Pathology, Hidaka Hospital, Gunma, Japan.

R Nishikawa (R)

Department of Neurosurgery, Graduate School of Medicine, Yokohama City University, Kanagawa, Japan.

M Matsutani (M)

Department of Neurosurgery, Graduate School of Medicine, Yokohama City University, Kanagawa, Japan.

K Ichimura (K)

Division of Brain Tumor Translational Research, National Cancer Center Research Institute, Tokyo, Japan.

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Classifications MeSH

questionsmedicales.fr › Maladies du système nerveux › Tumeurs du système nerveux › Tumeurs du système nerveux central › Tumeurs du cerveau › Intratumoural immune cell landscape in...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Reproduction › Développement embryonnaire et foetal › Développement embryonnaire › Lignage cellulaire › Intratumoural immune cell landscape in...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Intratumoural immune cell landscape in...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Tumeurs embryonnaires et germinales › Germinome › Intratumoural immune cell landscape in...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Intratumoural immune cell landscape in...
questionsmedicales.fr › Diagnostic › Pronostic › Intratumoural immune cell landscape in...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Intratumoural immune cell landscape in...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › Intratumoural immune cell landscape in...