Evidence map›Paper›PMID 35169141›Full record

ArticleNature communications2022

Re-engineered BCG overexpressing cyclic di-AMP augments trained immunity and exhibits improved efficacy against bladder cancer.

Alok Kumar Singh, Monali Praharaj, Kara A Lombardo, Takahiro Yoshida, Andres Matoso, Alex S Baras, Liang Zhao, Geetha Srikrishna, Joy Huang, Pankaj Prasad and 6 more

RetractedOpen access · goldAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
7.2field-weighted citation impact, top 2% 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

55 citing papers in PubMed, 94 citations in OpenAlex.

  1. Review
  2. Therapeutic bacteria-trained NK cells confer long-term protection against cancer metastasis.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  3. BCG HSP70 Reprograms Macrophages via Central Trained Immunity to Suppress Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Malevolent alliance of MYBL2Journal for immunotherapy of cancer · 2025
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 2 countries.

Alok Kumar SinghJohns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, MD, USA.
Monali PraharajJohns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, MD, USA.
Kara A LombardoJohns Hopkins University, School of Medicine, Department of Urology, Baltimore, MD, USA.
Takahiro YoshidaDepartment of Urology, Hyogo Prefectural Nishinomiya Hospital, Nishinomiya, 6620918, Japan.ORCID http://orcid.org/0000-0001-9468-7453
Andres MatosoDepartment of Pathology, The Johns Hopkins University, Baltimore, MD, USA.
Alex S BarasDepartment of Pathology, The Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-2397-3342
Liang ZhaoThe Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-2126-6778
Geetha SrikrishnaJohns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, MD, USA.
Joy HuangJohns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, MD, USA.
Pankaj PrasadJohns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, MD, USA.
Jonathan D PowellThe Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD, USA.
Max KatesJohns Hopkins University, School of Medicine, Department of Urology, Baltimore, MD, USA.
David McConkeyJohns Hopkins University, School of Medicine, Department of Urology, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-1971-0638
Drew M PardollThe Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD, USA.
William R BishaiJohns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, MD, USA. wbishai@jhmi.edu.ORCID http://orcid.org/0000-0002-8734-4118
Trinity J BivalacquaPerelman School of Medicine at the University of Pennsylvania, Division of Urology, Department of Surgery, Philadelphia, PA, USA. trinity.bivalacqua@pennmedicine.upenn.edu.
Johns Hopkins University · USBloomberg (United States) · USHyogo Prefectural Nishinomiya Hospital · JPUniversity of Pennsylvania · US

Funding

Mycobacterium tuberculosis Survival Regulatory GenesR01AI037856 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BISHAI, WILLIAM RAMSES · 1997 to 2020
$7.2M
NIAID NIH HHS R01 AI037856
6 · The paper itself

Abstract

In addition to its role as a TB vaccine, BCG has been shown to elicit heterologous protection against many other pathogens including viruses through a process termed trained immunity. Despite its potential as a broadly protective vaccine, little has been done to determine if BCG-mediated trained immunity levels can be optimized. Here we re-engineer BCG to express high levels of c-di-AMP, a PAMP recognized by stimulator of interferon genes (STING). We find that BCG overexpressing c-di-AMP elicits more potent signatures of trained immunity including higher pro-inflammatory cytokine responses, greater myeloid cell reprogramming toward inflammatory and activated states, and enhances epigenetic and metabolomic changes. In a model of bladder cancer, we also show that re-engineered BCG induces trained immunity and improved functionality. These results indicate that trained immunity levels and antitumor efficacy may be increased by modifying BCG to express higher levels of key PAMP molecules.

Indexed as

AnimalsBCG VaccineCancer VaccinesCD8-Positive T-LymphocytesCell Line, TumorCytokinesDinucleoside PhosphatesHumansImmunity, InnateMacrophagesMembrane ProteinsMiceMyeloid CellsPathogen-Associated Molecular Pattern MoleculesRatsSTING ProteinBCG VaccineCancer Vaccinescyclic diadenosine phosphateCytokinesDinucleoside PhosphatesMembrane ProteinsPathogen-Associated Molecular Pattern MoleculesSTING1 protein, humanSTING Protein

Identifiers

PMID35169141
PMCPMC8847416
OpenAlexW4213353617

What OpenQuestion holds

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LicenceCC BY
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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.