Evidence map›Paper›PMID 41666838›Full record

ArticleThe journal of physiological sciences : JPS2026

Orai1- and STIM1-mediated calcium signaling controls PD-L1 expression and modulates antitumor immunity in oral cancer.

Eriko Yamashita, Soichiro Ishikawa, Yuto Mizuno, Yu Iida, Mio Mochizuki, Akane Nagasako, Michiko Endo, Kohei Osawa, Yayoi Kimura, Takayuki Fujita and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The journal of physiological sciences : JPS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Eriko YamashitaCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan; Department of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan. Electronic address: erico@yokohama-cu.ac.jp.
Soichiro IshikawaDepartment of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan; Department of Clinical Oral Oncology, National hospital organization, Hokkaido Cancer Center, 3-54, 2-chome, Kikusui 4-jo, Shiroishi-ku, Sapporo-shi, Hokkaido 003-0804, Japan. Electronic address: soichisnsd@gmail.com.
Yuto MizunoDepartment of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan. Electronic address: mizuno.yut.wa@yokohama-cu.ac.jp.
Yu IidaCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan; Department of Neurosurgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan. Electronic address: iida.yu.wt@yokohama-cu.ac.jp.
Mio MochizukiCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan. Electronic address: e203074e@yokohama-cu.ac.jp.
Akane NagasakoCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan. Electronic address: nagasako@yokohama-cu.ac.jp.
Michiko EndoCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan. Electronic address: endo.mic.sd@yokohama-cu.ac.jp.
Kohei OsawaDepartment of Oral and Maxillofacial Surgery/Orthodontics, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama-shi, Kanagawa 232-0024, Japan. Electronic address: osawa.koh.eu@yokohama-cu.ac.jp.
Yayoi KimuraAdvanced Medical Research Center, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan. Electronic address: ykimura@yokohama-cu.ac.jp.
Takayuki FujitaDepartment of Physiology, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka-shi, Fukuoka 814-0180, Japan. Electronic address: utako@yokohama-cu.ac.jp.
Utako YokoyamaDepartment of Physiology, Tokyo Medical University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Electronic address: mitsudo@yokohama-cu.ac.jp.
Kenji MitsudoDepartment of Oral and Maxillofacial Surgery, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan. Electronic address: yishikaw@yokohama-cu.ac.jp.
Yoshihiro IshikawaYokohama City University President, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan.
Masanari UmemuraCardiovascular Research Institute, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama-shi, Kanagawa 236-0004, Japan. Electronic address: umemurma@yokohama-cu.ac.jp.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

This study investigated the regulation of PD-L1 expression by calcium signaling in oral squamous cell carcinoma (OSCC). We found that IFN-γ stimulation markedly altered the intracellular proteome and activated calcium-associated pathways. Pharmacological inhibition of store-operated calcium entry (SOCE) using the Orai1 inhibitor Synta66 suppressed IFN-γ-induced PD-L1 expression in a dose-dependent manner. Consistently, knockdown of Orai1 or STIM1 attenuated PD-L1 induction under IFN-γ stimulation, while basal expression remained unchanged. Inhibition of CaMK2 and CaMKK2 also reduced PD-L1 expression, indicating involvement of calmodulin-dependent kinase pathways. Functionally, Orai1 or STIM1 knockdown enhanced CD8⁺ T cell-mediated suppression of OSCC cell proliferation. Collectively, these results demonstrate that SOCE-mediated calcium signaling and downstream kinases regulate IFN-γ-induced PD-L1 expression and suggest that targeting SOCE components could represent a novel therapeutic approach to overcoming tumor immune evasion in OSCC. (132 words).

Indexed as

B7-H1 AntigenCalcium SignalingCarcinoma, Squamous CellMouth NeoplasmsNeoplasm ProteinsORAI1 ProteinStromal Interaction Molecule 1CalciumCalcium-Calmodulin-Dependent Protein Kinase KinaseCD8-Positive T-LymphocytesCell Line, TumorCell ProliferationHumansInterferon-gammaB7-H1 AntigenCalciumCalcium-Calmodulin-Dependent Protein Kinase KinaseCAMKK2 protein, humanCD274 protein, humanInterferon-gammaNeoplasm ProteinsORAI1 ProteinORAI1 protein, humanSTIM1 protein, humanStromal Interaction Molecule 1Interferon-gamma (IFN-γ)Oral squamous cell carcinoma (OSCC)PD-L1Store-operated calcium entry (SOCE)Tumor immune evasion

Identifiers

PMID41666838
PMCPMC12914183

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Registered trials

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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.