Evidence map›Paper›PMID 31285949›Full record

ArticleAmerican journal of cancer research2019

Temozolomide promotes immune escape of GBM cells via upregulating PD-L1.

Silu Wang, Fuli Yao, Xianghe Lu, Qun Li, Zhipeng Su, Jong-Ho Lee, Chengde Wang, Linyong Du

Open access · greenAbstract read
In one paragraph

Article in American journal of cancer research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

48 citing papers in PubMed, 69 citations in OpenAlex.

  1. Trial
  2. The Application of PD-1 Inhibitors in Immunotherapy for Glioblastoma.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Review
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  6. Dual-action nanotherapy: Temozolomide-loaded, anti-PD-L1 scFv-functionalized lipid nanocarriers for targeted glioblastoma therapy.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2025
    Article
  7. Article
  8. Review
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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

8 authors at 3 institutions in 2 countries.

Silu WangKey Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University Wenzhou 325000, Zhejiang, P. R. China.
Fuli YaoDepartment of Biochemistry and Molecular Biology, College of Preclinical Medicine, Southwest Medical University Luzhou, P. R. China.
Xianghe LuDepartment of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University Wenzhou 325000, Zhejiang, P. R. China.
Qun LiDepartment of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University Wenzhou 325000, Zhejiang, P. R. China.
Zhipeng SuDepartment of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University Wenzhou 325000, Zhejiang, P. R. China.
Jong-Ho LeeDepartment of Neuro-Oncology, The University of Texas MD Anderson Cancer Center Houston, Texas 77030, USA.
Chengde WangDepartment of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Medical University Wenzhou 325000, Zhejiang, P. R. China.
Linyong DuSchool of Laboratory Medicine and Life Science, Wenzhou Medical University Wenzhou 325035, Zhejiang, P. R. China.
Wenzhou Medical University · CNSouthwest Medical University · CNThe University of Texas MD Anderson Cancer Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor with poor prognosis, and currently effective therapeutic strategies are still limited. Although temozolomide (TMZ) is commonly used for GBM therapy and its mechanism was well characterized, while its side effects were required comprehensive investigation. In the present study, we revealed that TMZ-challenged GBM cells strongly suppressed pro-inflammatory cytokines expression in activated periphery blood mononuclear cells (PBMC), which depended on enhanced transcription of CD274 (encoding PD-L1), but not other immune checkpoints, such as CD276, HVEM and galectin-9. Moreover, abundance of membranous PD-L1 was also increased in TMZ-treated GBM cells. When PD-L1 expression was knocked down by short hairpin RNA (shRNA), inhibitory effect of TMZ-treated GBM cells on PBMC became weakened, suggesting that PD-L1 was crucial for immune inhibition capacity of TMZ-treated GBM cells. Additionally, actinomycin D reduced PD-L1 expression in GBM cells after TMZ challenge, indicating that PD-L1 induction occurred at transcriptional level. The immunoblotting results demonstrated that STAT3 signaling was involved in TMZ-mediated PD-L1 induction, and attenuated expression of PD-L1 was observed using STAT3 inhibitor VI or STAT3 shRNA. Finally, the animal study showed that combination of TMZ and PD-1 antibody therapy strongly inhibited tumor growth and achieved the improved survival rate of GBM mice. Accordingly, this study revealed the classical chemotherapy drug TMZ promoted GBM cells immune escape, even TMZ combine with PD-1 antibody treatment not further improve survival ratio of recurrent GBM patients compared with traditional therapy methods, while our animal study provided evidence that combination of TMZ and PD-1 antibody was a promising way to treat GBM, these contradictory results indicate improving the PD-1 antibody delivery efficiency can exert strong combinational therapy outcomes.

Indexed as

combinational therapyGBMimmune escapePD-L1temozolomide

Identifiers

PMID31285949
PMCPMC6610056
OpenAlexW2990257238

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.