Evidence map›Paper›PMID 40495489›Full record

ArticleBMB reports2025

Modulating CD226 and PD-(L)1 pathways improves CMV-specific CD8＋T cell responses in the absence of IL-2.

Hye-In Sim, Yunju Jo, Hyejin Ahn, Juyeon Hong, Hye-Bin Kim, Bohwan Yun, Haeun Son, Yeonjun Jeong, Jibaek Kim, Chan-Sik Park and 2 more

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Article in BMB reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Hye-In SimChemical and Biological Integrative Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792; Department of Life Sciences, Korea University, Seoul 02481, Korea.
Yunju JoChemical and Biological Integrative Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792; Department of Life Sciences, Korea University, Seoul 02481, Korea.
Hyejin AhnDepartment of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
Juyeon HongChemical and Biological Integrative Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792; Department of Life Sciences, Korea University, Seoul 02481, Korea.
Hye-Bin KimDepartment of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
Bohwan YunDepartment of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
Haeun SonDepartment of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
Yeonjun JeongDepartment of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
Jibaek KimDepartment of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
Chan-Sik ParkDepartment of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.
Yoon ParkChemical and Biological Integrative Research Center, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
Hyung-Seung JinDepartment of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma (GBM) frequently expresses cytomegalovirus (CMV) antigens, making CMV-specific CD8＋T cells attractive candidates for adoptive immunotherapy due to their longevity and inherent tumor reactivity. However, these T cells encounter significant immunosuppressive challenges within the GBM microenvironment, including cytokine scarcity and checkpointmediated inhibition, which limit their proliferation and function. Here, we assessed strategies to overcome these limitations by modulating immune checkpoint pathways. Antigen stimulation combined with IL-2 robustly expanded high-avidity (tetramer-high) CMV-specific T cells with significant enrichment of CD62L＋ central memory (TCM) cells. In contrast, antigen stimulation alone modestly expanded tetramer-high cells with limited TCM enrichment. PD-L1 blockade in the absence of IL-2 favored expansion of tetramer-high CMV-specific CD8＋T cells, preserved CD62L expression, and enhanced CD226 expression. Furthermore, combining anti-PD-L1 blockade with an anti-CD226 agonist markedly enhanced proliferation, IFN-γ production, and TCM enrichment in both tetramer-high and tetramer-low populations, reaching levels comparable to IL-2-supported conditions. Together, these findings highlight that simultaneous modulation of PD-L1 and CD226 pathways can restore CMV-specific T cell function, offering a promising strategy to boost TCR-T efficacy in cytokine-deprived environments. [BMB Reports 2025; 58(7): 307-312].

Indexed as

Antigens, Differentiation, T-LymphocyteB7-H1 AntigenCD8-Positive T-LymphocytesCytomegalovirusInterleukin-2GlioblastomaHumansImmunotherapy, AdoptiveAntigens, Differentiation, T-LymphocyteB7-H1 AntigenCD274 protein, humanInterleukin-2

Identifiers

PMID40495489
PMCPMC12313400

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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.