Evidence map›Paper›PMID 29147602›Full record

ArticleOncoimmunology

GDNF secreted by nerves enhances PD-L1 expression via JAK2-STAT1 signaling activation in HNSCC.

Chengzhong Lin, Wei Cao, Zhenhu Ren, Yu Tang, Chunye Zhang, Rong Yang, Yiming Chen, Zheqi Liu, Canbang Peng, Lizhen Wang and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 15% of its field
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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

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  12. Unraveling the role of glial cell line-derived neurotrophic factor in the treatment of Parkinson's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024
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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

12 authors at 1 institution in 1 country.

Chengzhong LinDepartment of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.
Wei CaoDepartment of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.
Zhenhu RenDepartment of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.
Yu TangDepartment of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.
Chunye ZhangDepartment of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Rong YangDepartment of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.
Yiming ChenDepartment of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.
Zheqi LiuDepartment of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.
Canbang PengDepartment of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.
Lizhen WangDepartment of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xu WangDepartment of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.
Tong JiDepartment of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, PR China.
Shanghai Jiao Tong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Programmed death ligand 1 (PD-L1) functions as a key immune inhibitory factor by binding with its receptor, programmed death 1 (PD-1), to induce immune cell dysfunction and escape of the immune system. However, the mechanisms of PD-L1 expression under growth factor stimulation are not well characterized. Here, we demonstrate a novel role for glial cell line-derived neurotrophic factor (GDNF) in upregulating PD-L1 expression in head and neck squamous cell carcinoma (HNSCC). The expression and correlation of PD-L1, GDNF and perineural invasion (PNI) status were evaluated by bioinformatics analysis of TCGA database and IHC assays from 145 HNSCC patients. PD-L1 expression was investigated by flow cytometry, Western blot and real-time PCR analyses in HNSCC cells after GNDF incubation. The cell signaling pathways activated by GDNF were analyzed with an antibody array and blocked by specific signaling inhibitors in cancer cell lines. PD-L1 expression was significantly higher in cancer cells that exhibited PNI in the HNSCC specimens, and elevated PD-L1 expression was significantly correlated with GDNF levels. GDNF not only enhanced cancer cell PNI in a co-culture of dorsal root ganglions and cancer cells but also had a potent role in inducing PD-L1 expression through the JAK2-STAT1 signaling pathway. Moreover, a JAK2 inhibitor attenuated GDNF-induced PD-L1 and enhanced tumor cell susceptibility to NK cell killing. Our findings provide clinically novel evidence that nerve-derived GDNF can increase PD-L1 levels in cancer cells around the perineural niche and that regulatory signaling is critical for cancer cell escape from immune surveillance in the nerve-cancer microenvironment.

Indexed as

GDNFHNSCCJAK2PD-L1PNI

Identifiers

PMID29147602
PMCPMC5674951
OpenAlexW2739237369

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.