Evidence map›Paper›PMID 31455836›Full record

ArticleCancer gene therapy2020

Synergistic antitumor effect on cervical cancer by rational combination of PD1 blockade and CRISPR-Cas9-mediated HPV knockout.

Shuai Zhen, Jiaojiao Lu, Yun-Hui Liu, Wei Chen, Xu Li

Abstract read
PubMed Publisher
In one paragraph

Article in Cancer gene therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

34 citing papers in PubMed, 52 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Towards the elimination of infectious HPV: exploiting CRISPR/Cas innovations.Frontiers in cellular and infection microbiology · 2025
    Review
  9. Harnessing the evolving CRISPR/Cas9 for precision oncology.Journal of translational medicine · 2024
    Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. CRISPR/Cas9 for hepatitis B virus infection treatment.Immunity, inflammation and disease · 2023
    Review
  16. Review
  17. Review
  18. Review
  19. Article
  20. Review
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

5 authors at 3 institutions in 1 country.

Shuai Zhen *Center for Translational Medicine, Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Jiaojiao Lu *Center for Translational Medicine, Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Yun-Hui LiuDepartment of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, China.
Wei ChenCenter of Laboratory Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Xu LiCenter for Translational Medicine, Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. lixu56@mail.xjtu.edu.cn.
First Affiliated Hospital of Xi'an Jiaotong University · CNNorthwest Women's and Children's Hospital · CNBeijing Radiation Center · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Targeted therapy results in objective responses in cervical cancer. However, the responses are short. In contrast, treatment with immune checkpoint inhibitors results in a lower responses rate, but the responses tend to be more durable. Based on these findings, we hypothesized that HPV16 E6/E7-targeted therapy may synergize with the PD-1 pathway blockade to enhance antitumor activity. To test hypothesis, we described for the first time the effects of the CRISPR/Cas9 that was targeted to the HPV and PD1 in vitro and in vivo. Our data showed that gRNA/cas9 targeted HPV16 E6/E7 induced cervical cancer cell SiHa apoptosis, and suggested that overexpression of PD-L1, induced by HPV16 E6/E7, may be responsible for lymphocyte dysfunction. In established SiHa cell- xenografted humanized SCID mice, Administration of gRNA-PD-1 together with gRNA-HPV16 E6/E7 treatment improved the survival and suppressed the tumor growth obviously. In addition, combination treatment increased the population of dendritic cells, CD8+ and CD4+ T lymphocyte cells. According, it enhanced the expression of Th1-associated immune-stimulating genes while reducing the transcription of regulatory/suppressive immune genes, reshaping tumor microenvironment from an immunosuppressive to a stimulatory state. These results demonstrate potent synergistic effects of combination therapy using HPV16 E6/E7-targeted therapy and immune checkpoint blockade PD1, supporting a direct translation of this combination strategy in clinic for the treatment of cervical cancer.

Indexed as

AnimalsApoptosisB7-H1 AntigenCell Line, TumorCombined Modality TherapyCRISPR-Cas SystemsFemaleGene Knockout TechniquesGenetic TherapyGenetic VectorsHuman papillomavirus 16HumansMiceOncogene Proteins, ViralPapillomavirus E7 ProteinsPapillomavirus InfectionsB7-H1 AntigenCD274 protein, humanE6 protein, Human papillomavirus type 16oncogene protein E7, Human papillomavirus type 16Oncogene Proteins, ViralPapillomavirus E7 ProteinsRepressor ProteinsRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID31455836
OpenAlexW2971163283

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.