Evidence map›Paper›PMID 40344445›Full record

ArticleCancer science2025

Immunosuppressive Effects of Multiple Myeloma-Derived Extracellular Vesicles Through T Cell Exhaustion.

Shinya Hagiwara, Masaki Ri, Toru Ebina, Yoshiaki Marumo, Tomoyuki Nakamura, Kentaro Hirade, Takahiro Nakashima, Arisa Asano, Shiori Kinoshita, Tomotaka Suzuki and 4 more

Abstract read
In one paragraph

Article in Cancer science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. PD-L1Biomarker research · 2026
    Article
  2. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Shinya HagiwaraDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan.ORCID https://orcid.org/0009-0000-7730-2531
Masaki RiDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan.ORCID https://orcid.org/0000-0002-9617-486X
Toru EbinaDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan.ORCID https://orcid.org/0009-0000-4341-9563
Yoshiaki MarumoDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan.
Tomoyuki NakamuraDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan.
Kentaro HiradeDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan.
Takahiro NakashimaDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan.
Arisa AsanoDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan.
Shiori KinoshitaDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan.
Tomotaka SuzukiDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan.
Tomoko NaritaDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan.
Ayako MasakiDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan.
Hirokazu KomatsuDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan.
Shinsuke IidaDepartment of Hematology and Oncology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan.ORCID https://orcid.org/0000-0002-4951-960X

Funding

The National Cancer Center Research and Development Fund 2020-J-3The National Cancer Center Research and Development Fund 2023-J-3
6 · The paper itself

Abstract

Extracellular vehicles (EVs) are reported to be involved in several processes relating to tumor progression, including angiogenesis, osteolysis, and drug resistance in multiple myeloma (MM). However, the role of EVs in the immune-suppressive milieu of MM is poorly understood. Here, we investigated the effects of MM-derived EVs on T cells, focusing on markers of T cell exhaustion. Using activated peripheral blood mononuclear cells from healthy donors, we observed immunosuppressive effects such as upregulated expression of immune checkpoint markers on CD8+ T cells treated with MM-derived EVs. Proteomic analysis identified several proteins, such as IL-8, SLC1A5, PIN2, and FSP1, associated with regulation of T cell exhaustion and chronic inflammation. Surprisingly, sphingosine kinase 1 (SPHK1) was enriched in MM cell line-derived EVs, implicating SPHK1/S1P signaling in the immunosuppressive effect of MM EVs. Thus, MM-derived EVs may promote T cell exhaustion via upregulating the expression of immune checkpoint markers and thereby contribute to the formation of the immune-suppressive milieu of MM, resulting in impaired T cell activity.

Indexed as

CD8-Positive T-LymphocytesExtracellular VesiclesMultiple MyelomaT-LymphocytesCell Line, TumorHumansImmune Checkpoint ProteinsLysophospholipidsPhosphotransferases (Alcohol Group Acceptor)ProteomicsSignal TransductionSphingosineSphingosine KinaseT-Cell ExhaustionImmune Checkpoint ProteinsLysophospholipidsPhosphotransferases (Alcohol Group Acceptor)Sphingosinesphingosine 1-phosphateSphingosine Kinaseextracellular vesiclesimmune checkpoint proteinsmultiple myelomasphingosine kinase 1T‐cell exhaustion

Identifiers

PMID40344445
PMCPMC12210033

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.