Evidence map›Paper›PMID 31802034›Full record

ArticleCell death and differentiation2020

Macrophage-derived CCL5 facilitates immune escape of colorectal cancer cells via the p65/STAT3-CSN5-PD-L1 pathway.

Chao Liu, Zhaoying Yao, Jianing Wang, Wen Zhang, Yan Yang, Yan Zhang, Xinliang Qu, Yubing Zhu, Jianjun Zou, Sishi Peng and 7 more

Erratum issuedAbstract read
In one paragraph

Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 150 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
150citing papers in PubMed, 1 pooled it
–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

150 citing papers in PubMed, 1 synthesis or guideline pooled it.

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90 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Chao Liu *Department of Pharmacy, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, PR China.
Zhaoying Yao *Department of Pharmacy, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, PR China.
Jianing Wang *Neurobiology Laboratory, Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, 210009, PR China.
Wen ZhangDepartment of Pharmacy, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, PR China.
Yan YangDepartment of Pharmacy, The Third People's Hospital of Chengdu & Affiliated Hospital of Southwest Jiaotong University, 82 Qing Long Street, Chengdu, 610031, PR China.
Yan ZhangDepartment of Gastroenterology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, PR China.
Xinliang QuDepartment of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, PR China.
Yubing ZhuDepartment of Pharmacy, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, PR China.
Jianjun ZouDepartment of Pharmacy, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, PR China.
Sishi PengDepartment of Clinical Pharmacy, School of Basic Medicine & Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, PR China.
Yan ZhaoDepartment of Pharmacy, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, PR China.
Shuli ZhaoGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, PR China.
Bangshun HeGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, PR China.
Qiongyu MiGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, PR China.
Xiuting LiuDepartment of Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Xu ZhangDepartment of Pharmacy, The First People's Hospital of Chengdu & Affiliated Hospital of Chengdu Medical College, 18 Wanxiang East Road, Chengdu, 610041, PR China. Jason151X7@stu.cpu.edu.cn.
Qianming DuGeneral Clinical Research Center, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, PR China. duqianming@njmu.edu.cn.ORCID http://orcid.org/0000-0002-1092-2899

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Infiltrated macrophages are an important constituent of the tumor microenvironment and play roles in tumor initiation and progression by promoting immune evasion. However, the molecular mechanism by which macrophage-derived cytokines foster immune escape of colorectal cancer (CRC) is unclear. Here, we demonstrated that macrophage infiltration induced by lipopolysaccharide (LPS) or a high-cholesterol diet (HCD) significantly promoted CRC growth. Similarly, LPS and poly (I:C) remarkably increased the volume of CT26 cell allograft tumors. C-C motif chemokine ligand 5 (CCL5), which is secreted by macrophages, inhibited T-cell-mediated killing of HT29 cells and promoted immune escape by stabilizing PD-L1 in vitro and in vivo. Mechanistically, CCL5 resulted in formation of nuclear factor kappa-B p65/STAT3 complexes, which bound to the COP9 signalosome 5 (CSN5) promoter, leading to its upregulation. Moreover, CSN5 modulated the deubiquitination and stability of PD-L1. High expression of CSN5 in CRC was associated with significantly shorter survival. Furthermore, compound-15 was identified as an inhibitor of CSN5, and destabilized PD-L1 to alleviate the tumor burden. Our results suggest that the novel CCL5-p65/STAT3-CSN5-PD-L1 signaling axis is significantly activated by LPS or HCD-driven macrophage infiltration in an animal model of CRC, which likely has therapeutic and prognostic implications for human cancers.

Indexed as

AnimalsCell Line, TumorChemokine CCL5Colorectal NeoplasmsHumansIntracellular Signaling Peptides and ProteinsMacrophagesMaleMiceMice, Inbred C57BLNeoplasm ProteinsSTAT3 Transcription FactorCCL5 protein, humanChemokine CCL5HSAJ2425 protein, humanIntracellular Signaling Peptides and ProteinsNeoplasm ProteinsSTAT3 protein, humanSTAT3 Transcription Factor

Identifiers

PMID31802034
PMCPMC7244707

What OpenQuestion holds

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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.