Evidence map›Paper›PMID 42845663›Full record

ArticlebioRxiv : the preprint server for biology2026

Targeting Tumor-derived Sphingosine Kinase 2 Unleashes Antitumor Immunity and Improves Survival of Mice with Group 3 Medulloblastoma.

Sampurna Chatterjee, Pragya Kumar, Ashwin S Kumar, Pin-Ji Lei, Meenal Datta, Yuhui Zhao, William W Ho, Nilesh P Talele, Patrik Andersson, Mark Duquette and 12 more

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

22 authors.

Sampurna ChatterjeeEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0003-0850-0328
Pragya KumarEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
Ashwin S KumarEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
Pin-Ji LeiEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0003-2539-5179
Meenal DattaEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0001-5727-8992
Yuhui ZhaoEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
William W HoEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0002-1272-8184
Nilesh P TaleleEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0003-2758-8599
Patrik AnderssonEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
Mark DuquetteEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
Shuji KitaharaEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0002-2904-0319
Landry BlancPublic Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, USA.; Veronique Dartois Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA.
Samantha J WongDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Wilhelmus J KwantenEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0001-9474-6695
David H EbbDepartment of Pediatric Hematology/Oncology, Mass General Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Torunn I YockFrancis H. Burr Proton Therapy Center, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0001-6408-8011
Veronique DartoisPublic Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey 07103, USA.; Veronique Dartois Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA.ORCID 0000-0001-9470-5009
Dai FukumuraEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0002-9505-4444
Dan G DudaEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0001-7065-8797
Lei XuEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
Hye-Jung KimDepartment of Immunology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.ORCID 0009-0001-3519-4541
Rakesh K JainEdwin L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
Targeting physical stress-driven mechanisms to overcome glioblastoma treatment resistanceU01CA261842 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K., MUNN, LANCE L. · 2021 to 2025
$3.1M
Reprogramming PDAC tumor microenvironment to improve immunotherapyU01CA224348 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BOUCHER, YVES, JAIN, RAKESH K. · 2017 to 2021
$2.9M
Multiplexed time domain fluorescence tomography of tumor biomarkers during immunotherapyR01CA260857 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Dan Gabriel Duda, Anand T.N. Kumar · 2021 to 2026
$2.7M
Improving treatment of HER2+ breast cancer brain metastasis by targeting lipid metabolismR01CA259253 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K., VANDER HEIDEN, MATTHEW G. · 2021 to 2025
$2.3M
Reengineering obesity-induced abnormal microenvironment to improve PDAC treatmentR01CA208205 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI FUKUMURA, DAI, JAIN, RAKESH K. · 2017 to 2020
$2.2M
Reprogramming the Tumor Microenvironment to Improve Immunotherapy of Glioblastoma by Co-Targeting VEGF and Ang2R01NS118929 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI FUKUMURA, DAI · 2021 to 2025
$2.0M
Defining Optimal Radiotherapy Dose and Fractionation in Combination with Preoperative Immuno-Chemotherapy in Early-Stage Triple Negative Breast CancerR01CA274254 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Dana Casey, Dan Gabriel Duda · 2023 to 2026
$840k
NCI NIH HHS P30 CA014051NCI NIH HHS R01 CA208205NCI NIH HHS R01 CA259253NCI NIH HHS R01 CA260857NCI NIH HHS R01 CA274254NCI NIH HHS U01 CA224348NCI NIH HHS U01 CA261842NINDS NIH HHS R01 NS118929
6 · The paper itself

Abstract

Group 3 medulloblastomas (G3MB) carry the worst prognosis among medulloblastoma subtypes, yet molecularly targeted therapies remain elusive. Standard treatments cause severe long-term morbidity in survivors. Here, we identify tumor-derived sphingosine kinase 2 (SPHK2) as an essential driver of G3MB initiation and progression. SPHK2 exacerbates local immunosuppression by suppressing cytotoxic T-cell and NK-cell activity while promoting regulatory T-cell infiltration. Genetic or pharmacologic SPHK2 inhibition using Opaganib attenuates pro-survival tumor signaling and restores anti-tumor immunity, significantly improving survival in syngeneic G3MB mouse models. Combining Opaganib with fractionated low-dose radiation (f-LDRT) further enhances antigen presentation and reprograms tumor-associated myeloid cells toward an anti-tumor phenotype. This combination therapy markedly prolongs survival without inducing significant toxicity. Overall, our study establishes SPHK2 as a previously unrecognized therapeutic target and presents a safe, effective, microenvironment-reprogramming regimen for G3MB.

Identifiers

PMID42845663
PMCPMC13640785

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