Evidence map›Paper›PMID 39872623›Full record

ArticleLife metabolism2023

Blockade of Arf1-mediated lipid metabolism in cancers promotes tumor infiltration of cytotoxic T cells via the LPE-PPARγ-NF-κB-CCL5 pathway.

Na Wang, Tiange Yao, Chenfei Luo, Ling Sun, Yuetong Wang, Steven X Hou

Abstract read
In one paragraph

Article in Life metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

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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

6 authors.

Na WangDepartment of Cell and Developmental Biology at School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Fudan University, Shanghai 200438, China.
Tiange YaoDepartment of Cell and Developmental Biology at School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Fudan University, Shanghai 200438, China.
Chenfei LuoDepartment of Cell and Developmental Biology at School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Fudan University, Shanghai 200438, China.
Ling SunDepartment of Cell and Developmental Biology at School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Fudan University, Shanghai 200438, China.
Yuetong WangDepartment of Cell and Developmental Biology at School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Fudan University, Shanghai 200438, China.
Steven X HouDepartment of Cell and Developmental Biology at School of Life Sciences, State Key Laboratory of Genetic Engineering, Institute of Metabolism and Integrative Biology, Human Phenome Institute, Fudan University, Shanghai 200438, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tumor immunotherapy has achieved breakthroughs in a variety of tumors. However, the systemic absence of T cells in tumors and immunosuppressive tumor microenvironment so far limits the efficacy of immunotherapy to a small population of patients. Therefore, novel agents to increase T-cell tumor infiltration are urgently needed in the clinic. We recently found that inhibition of the ADP-ribosylation factor 1 (Arf1)-mediated lipid metabolism not only kills cancer stem cells (CSCs) but also elicits an anti-tumor immune response. In this study, we revealed a mechanism that targeting Arf1 promotes the infiltration of cytotoxic T lymphocytes (CTLs) into tumors through the C-C chemokine ligand 5 (CCL5)- C-C chemokine receptor type 5 (CCR5) pathway. We found that blockage of Arf1 induces the production of the unsaturated fatty acid (PE 18:1) that binds and sequestrates peroxisome proliferator--activated receptor-γ (PPARγ) from the PPARγ-nuclear factor-κB (NF-κB) cytoplasmic complex. The released NF-κB was then phosphorylated and translocated into the nucleus to regulate the transcription of chemokine CCL5. CCL5 promoted infiltration of CTLs for tumor regression. Furthermore, the combination of the Arf1 inhibitor and programmed cell death protein 1 (PD-1) blockade induced an even stronger anti-tumor immunity. Therefore, targeting Arf1 represents a novel anti-tumor immune approach by provoking T-cell tumor infiltration and may provide a new strategy for tumor immunotherapy.

Indexed as

Arf1cancer stem cellsCCL5-CCR5 pathwaycytotoxic T cellsimmune checkpoint blockadePPARγ

Identifiers

PMID39872623
PMCPMC11749100

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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.