Evidence map›Paper›PMID 41541220›Full record

ArticleNeuro-oncology advances

Preclinical assessment of checkpoint blockade combined with DNA methyltransferase inhibition in high-risk pediatric brain tumors reveals limited therapeutic synergy.

Deepak Kumar Mishra, Shelli M Morris, Dean Popovski, Emily J Girard, Andrew Bondoc, Shiva Senthil Kumar, Augusto Faria Andrade, Xiaoting Zhu, Fupan Yao, Mi-Youn Brusniak and 19 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. 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

29 authors.

Deepak Kumar MishraCenter for Childhood Cancer Research, Nationwide Children's Hospital, Columbus (D.K.M., S.S.K., X.Z., B.U., R.D.).
Shelli M MorrisThe Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children's Research Institute, Seattle (S.M.M., E.J.G., E.E.C., K.B., M.C.B., H.C., J.M.O.).ORCID https://orcid.org/0000-0001-6397-0117
Dean PopovskiDivision of Haematology/Oncology, Hospital for Sick Children, Department of Pediatrics, Arthur and Sonia Labatt Brain Tumor Research Centre, University of Toronto, Toronto, Canada (D.P., A.B., F.Y., M.L., A.H.).ORCID https://orcid.org/0000-0001-9239-2141
Emily J GirardThe Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children's Research Institute, Seattle (S.M.M., E.J.G., E.E.C., K.B., M.C.B., H.C., J.M.O.).ORCID https://orcid.org/0000-0002-7791-3639
Andrew BondocDivision of Haematology/Oncology, Hospital for Sick Children, Department of Pediatrics, Arthur and Sonia Labatt Brain Tumor Research Centre, University of Toronto, Toronto, Canada (D.P., A.B., F.Y., M.L., A.H.).ORCID https://orcid.org/0000-0003-1468-6245
Shiva Senthil KumarCenter for Childhood Cancer Research, Nationwide Children's Hospital, Columbus (D.K.M., S.S.K., X.Z., B.U., R.D.).ORCID https://orcid.org/0000-0002-8546-9734
Augusto Faria AndradeDepartment of Human Genetics, McGill University, Montreal, Canada (A.F.A., C.R., M.Z., N.J.).ORCID https://orcid.org/0000-0001-5866-0501
Xiaoting ZhuCenter for Childhood Cancer Research, Nationwide Children's Hospital, Columbus (D.K.M., S.S.K., X.Z., B.U., R.D.).
Fupan YaoDivision of Haematology/Oncology, Hospital for Sick Children, Department of Pediatrics, Arthur and Sonia Labatt Brain Tumor Research Centre, University of Toronto, Toronto, Canada (D.P., A.B., F.Y., M.L., A.H.).ORCID https://orcid.org/0009-0005-7021-2206
Mi-Youn BrusniakClinical Research Division, Fred Hutchinson Cancer Center, Seattle (M.-Y.B., E.E.C., F.P., Ma.C., Mi.C., J.M.O.).ORCID https://orcid.org/0000-0003-3950-1614
Banlanjo UmaruCenter for Childhood Cancer Research, Nationwide Children's Hospital, Columbus (D.K.M., S.S.K., X.Z., B.U., R.D.).ORCID https://orcid.org/0000-0003-4517-2255
Erin E CrottyThe Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children's Research Institute, Seattle (S.M.M., E.J.G., E.E.C., K.B., M.C.B., H.C., J.M.O.).
Ken BraselThe Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children's Research Institute, Seattle (S.M.M., E.J.G., E.E.C., K.B., M.C.B., H.C., J.M.O.).
Fiona PakiamClinical Research Division, Fred Hutchinson Cancer Center, Seattle (M.-Y.B., E.E.C., F.P., Ma.C., Mi.C., J.M.O.).ORCID https://orcid.org/0000-0001-6292-1137
Caterina RussoDepartment of Human Genetics, McGill University, Montreal, Canada (A.F.A., C.R., M.Z., N.J.).
Michele ZeiniehDepartment of Human Genetics, McGill University, Montreal, Canada (A.F.A., C.R., M.Z., N.J.).ORCID https://orcid.org/0000-0002-0875-2077
Matt C BieryThe Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children's Research Institute, Seattle (S.M.M., E.J.G., E.E.C., K.B., M.C.B., H.C., J.M.O.).
Margo CoxonClinical Research Division, Fred Hutchinson Cancer Center, Seattle (M.-Y.B., E.E.C., F.P., Ma.C., Mi.C., J.M.O.).ORCID https://orcid.org/0000-0001-6712-8752
Heather ContiThe Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children's Research Institute, Seattle (S.M.M., E.J.G., E.E.C., K.B., M.C.B., H.C., J.M.O.).ORCID https://orcid.org/0000-0002-1491-4212
Midori ClarkeClinical Research Division, Fred Hutchinson Cancer Center, Seattle (M.-Y.B., E.E.C., F.P., Ma.C., Mi.C., J.M.O.).ORCID https://orcid.org/0000-0002-2402-108X
Mei LuDivision of Haematology/Oncology, Hospital for Sick Children, Department of Pediatrics, Arthur and Sonia Labatt Brain Tumor Research Centre, University of Toronto, Toronto, Canada (D.P., A.B., F.Y., M.L., A.H.).
James RutkaDivision of Neurosurgery, Hospital for Sick Children, Toronto, Canada (J.R.).ORCID https://orcid.org/0000-0003-0851-7330
Dhana Llivichuzhca-LojaDepartment of Pediatrics, Yale School of Medicine, New Haven (D.L.-L., L.K.).
Liza KonnikovaDepartment of Pediatrics, Yale School of Medicine, New Haven (D.L.-L., L.K.).
Maryam FouladiPediatric Neuro-Oncology Program, Nationwide Children's Hospital, Columbus (M.F.).ORCID https://orcid.org/0009-0005-3039-3313
Nada JabadoDepartment of Human Genetics, McGill University, Montreal, Canada (A.F.A., C.R., M.Z., N.J.).ORCID https://orcid.org/0000-0003-2485-3692
Annie HuangDivision of Haematology/Oncology, Hospital for Sick Children, Department of Pediatrics, Arthur and Sonia Labatt Brain Tumor Research Centre, University of Toronto, Toronto, Canada (D.P., A.B., F.Y., M.L., A.H.).
James M OlsonThe Ben Towne Center for Childhood Cancer and Blood Disorders Research, Seattle Children's Research Institute, Seattle (S.M.M., E.J.G., E.E.C., K.B., M.C.B., H.C., J.M.O.).
Rachid DrissiCenter for Childhood Cancer Research, Nationwide Children's Hospital, Columbus (D.K.M., S.S.K., X.Z., B.U., R.D.).ORCID https://orcid.org/0000-0003-0564-0181

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Abstract: BackgroundDespite intensive therapies, outcomes for high-risk pediatric brain tumors (PBTs) remain dismal, prompting the search for novel treatments. DNA methyltransferase inhibitors (DNMTi) have been shown to prime tumors to improve response to checkpoint inhibition. The aim of this study was to investigate the potential of decitabine (DAC), in combination with a PD-1 inhibitor, to improve survival in pediatric high-risk brain tumor models. Methods: Analysis of human PBT datasets was performed to determine gene expression levels of immune cell markers. Tumor response to DAC, with or without a PD-1 inhibitor, was tested in murine models representing H3-wildtype diffuse intrinsic pontine glioma (DIPG), H3K27-mutant diffuse midline glioma (DMG), atypical teratoid rhabdoid tumor (ATRT), and medulloblastoma (MB). CyTOF analysis of allograft tumors was performed to characterize changes within the tumor microenvironment. Results: Analysis of PBT subtypes revealed heterogeneous expression of immune cell markers, checkpoint receptors, and MHC molecules. DAC treatment decreased DNA methylation and increased neoantigen expression in human and mouse tumor cells. DAC treatment resulted in prolonged survival in syngeneic mouse models of DIPG and ATRT but not DMG and MB models. However, no added survival benefit was observed when combined with a PD-1 inhibitor. CyTOF analysis of mouse tumors revealed changes in local immune cell infiltration. Conclusions: DAC alone or in combination with a checkpoint inhibitor can alter the immune microenvironment in mouse tumor models. Changes were observed in H3-wildtype DIPG and ATRT models, suggesting that certain tumor subtypes may respond to immune priming with DNMTi.

Indexed as

epigenetic modifiersimmune checkpoint inhibitors (ICIs)neoantigenpediatric brain tumors (PBTs)preclinical models

Identifiers

PMID41541220
PMCPMC12803780

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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.