Evidence map›Paper›PMID 22666458›Full record

ArticlePloS one2012

An in situ autologous tumor vaccination with combined radiation therapy and TLR9 agonist therapy.

Huagang Zhang, Laibin Liu, Dong Yu, Ekambar R Kandimalla, Hui Bin Sun, Sudhir Agrawal, Chandan Guha

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 18% 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

35 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Myeloid MyD88 restricts CD8Scientific reports · 2023
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  7. Therapeutic applications of toll-like receptors (TLRs) agonists in AML.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022
    Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Immune Checkpoint Blockade in Combination with Stereotactic Body Radiotherapy in Patients with Metastatic Pancreatic Ductal Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Article
  14. Effects of Radiation on the Tumor Microenvironment.Seminars in radiation oncology · 2020
    Review
  15. Toll-Like Receptor 9 Agonists in Cancer.OncoTargets and therapy · 2020
    Review
  16. Review
  17. Time for radioimmunotherapy: an overview to bring improvements in clinical practice.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2019
    Review
  18. Article
  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

7 authors at 3 institutions in 1 country.

Huagang ZhangDepartment of Radiation Oncology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York, United States of America.
Laibin Liu
Dong Yu
Ekambar R Kandimalla
Hui Bin Sun
Sudhir Agrawal
Chandan Guha
Albert Einstein College of Medicine · USIdera Pharmaceuticals (United States) · USMontefiore Medical Center · US

Funding

Stem Cell-Based Therapies for Radiation-Induced Gastrointestinal Sydrome (RIGS)U19AI091175 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI GUHA, CHANDAN · 2010 to 2014
$13.1M
HIFU-enhanced tumor vaccinesR01EB009040 · NIBIB · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI GUHA, CHANDAN · 2008 to 2012
$2.2M
Preparative irradiation for hepatocyte transplantationR01DK064670 · NIDDK · ALBERT EINSTEIN COL OF MED YESHIVA UNIV · PI GUHA, CHANDAN · 2005 to 2009
$1.9M
Stem Cell Based Therapy For Radiation Induced Gastrointestinal SyndromeRC2AI087612 · NIAID · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI GUHA, CHANDAN · 2010 to 2010
$578k
NIAID NIH HHS RC2 AI087612NIAID NIH HHS U19 AI091175NIAID NIH HHS U19AI091175NIBIB NIH HHS R01 EB009040NIBIB NIH HHS R01EB009040NIDDK NIH HHS R01 DK064670NIDDK NIH HHS R01DK064670
6 · The paper itself

Abstract

purposeRecent studies have shown that a new generation of synthetic agonist of Toll-like receptor (TLR) 9 consisting a 3'-3'-attached structure and a dCp7-deaza-dG dinucultodie shows more potent immunostimulatory effects in both mouse and human than conventional CpG oligonucleotides. Radiation therapy (RT) provides a source of tumor antigens that are released from dying, irradiated, tumor cells without causing systemic immunosuppression. We, therefore, examined effect of combining RT with a designer synthetic agonist of TLR9 on anti-tumoral immunity, primary tumor growth retardation and metastases in a murine model of lung cancer.

methodsGrouped C57BL/6 and congenic B cell deficient mice (B(-/-)) bearing footpad 3LL tumors were treated with PBS, TLR9 agonist, control oligonucelotide, RT or the combination of RT and TLR9 agonist. Immune phenotype of splenocytes and serum IFN-γ and IL-10 levels were analyzed by FACS and ELISA, 24 h after treatment. Tumor growth, lung metastases and survival rate were monitored and tumor specific antibodies in serum and deposition in tumor tissue were measured by ELISA and immunofluorescence.

resultsTLR9 agonist expanded and activated B cells and plasmacytoid dendritic cells in wild-type mice and natural killer DCs (NKDCs) in B cell-deficient (B(-/-)) mice bearing ectopic Lewis lung adenocarcinoma (3LL). Combined RT with TLR9 agonist treatment inhibited 3LL tumor growth in both wild type and B(-/-) mice. A strong tumor-specific humoral immune response (titer: 1/3200) with deposition of mouse IgG auto-antibodies in tumor tissue were found in wildtype mice, whereas the number of tumor infiltrating NKDCs increased in B(-/-) mice following RT+ TLR9 agonist therapy. Furthermore, mice receiving combination therapy had fewer lung metastases and a higher survival than single treatment cohorts.

conclusionsCombination therapy with TLR9 agonist and RT induces systemic anti-tumoral humoral response, augments tumoral infiltration of NKDCs, reduces pulmonary metastases and improves survival in a murine model of 3LL cancer.

Indexed as

VaccinationAdenocarcinomaAdenocarcinoma of LungAnimalsAntibodies, NeoplasmAntigens, NeoplasmAntineoplastic AgentsB-LymphocytesCell Line, TumorCombined Modality TherapyDendritic CellsDisease ProgressionHumansImmunomodulationLung NeoplasmsMaleAntibodies, NeoplasmAntigens, NeoplasmAntineoplastic AgentsToll-Like Receptor 9

Identifiers

PMID22666458
PMCPMC3364192
OpenAlexW1965805984

What OpenQuestion holds

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LicenceCC BY
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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.