Evidence map›Paper›PMID 40403728›Full record

ArticleCell2025

Serotonin transporter inhibits antitumor immunity through regulating the intratumoral serotonin axis.

Bo Li, James Elsten-Brown, Miao Li, Enbo Zhu, Zhe Li, Yuning Chen, Elliot Kang, Feiyang Ma, Jennifer Chiang, Yan-Ruide Li and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.

0numbers the graph read from it
0cells of the map it votes in
51citing 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

51 citing papers in PubMed.

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  5. Low-Dose Intestinal Irradiation Enhances the Efficacy and Prognosis of PD-1 Blockade in Metastatic Non-Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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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

19 authors.

Bo LiDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: bo.li@ucla.edu.
James Elsten-BrownDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Miao LiDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Enbo ZhuDepartment of Materials Science and Engineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Zhe LiDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Yuning ChenDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Elliot KangDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Feiyang MaDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jennifer ChiangDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Yan-Ruide LiDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Yichen ZhuDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jie HuangDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Audrey FungDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Quentin ScarboroughDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Robin CaddDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Jin J ZhouDepartment of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA.
Arnold I ChinDepartment of Urology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Matteo PellegriniDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Quantitative and Computational Biosciences-The Collaboratory, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Lili YangDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; Goodman-Luskin Microbiome Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA; Parker Institute for Cancer Immunotherapy, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: liliyang@ucla.edu.

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
UCLA Tumor Immunology Training ProgramT32CA009120 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Steven M. Dubinett, MICHAEL A TEITELL · 1985 to 2026
$10.3M
UCLA and Caltech integrated Cardiovascular Medicine for Bioengineers (iCMB)T32HL144449 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HSIAI, TZUNG K, PAJUKANTA, PAIVI · 2020 to 2024
$1.2M
NCATS NIH HHS UL1 TR001881NCI NIH HHS T32 CA009120NHLBI NIH HHS T32 HL144449
6 · The paper itself

Abstract

Identifying additional immune checkpoints hindering antitumor T cell responses is key to the development of next-generation cancer immunotherapies. Here, we report the induction of serotonin transporter (SERT), a regulator of serotonin levels and physiological functions in the brain and peripheral tissues, in tumor-infiltrating CD8 T cells. Inhibition of SERT using selective serotonin reuptake inhibitors (SSRIs), the most widely prescribed antidepressants, significantly suppressed tumor growth and enhanced T cell antitumor immunity in various mouse syngeneic and human xenograft tumor models. Importantly, SSRI treatment exhibited significant therapeutic synergy with programmed cell death protein 1 (PD-1) blockade, and clinical data correlation studies negatively associated intratumoral SERT expression with patient survival in a range of cancers. Mechanistically, SERT functions as a negative-feedback regulator inhibiting CD8 T cell reactivities by depleting intratumoral T cell-autocrine serotonin. These findings highlight the significance of the intratumoral serotonin axis and identify SERT as an immune checkpoint, positioning SSRIs as promising candidates for cancer immunotherapy.

Indexed as

NeoplasmsSerotoninSerotonin Plasma Membrane Transport ProteinsAnimalsCD8-Positive T-LymphocytesCell Line, TumorFemaleHumansImmunotherapyMiceMice, Inbred C57BLProgrammed Cell Death 1 ReceptorSelective Serotonin Reuptake InhibitorsProgrammed Cell Death 1 ReceptorSelective Serotonin Reuptake InhibitorsSerotoninSerotonin Plasma Membrane Transport Proteinsantidepressantscancer immunotherapyimmune checkpointintratumoral serotonin axisPD-1 blockadeserotoninserotonin transporterSSRIsT cell antitumor immunitytumor microenvironment

Identifiers

PMID40403728
PMCPMC12255530

What OpenQuestion holds

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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.