Evidence map›Paper›PMID 41619263›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Cellular Identity Crisis: RD3 Loss Fuels Plasticity and Immune Silence in Progressive Neuroblastoma.

Poorvi Subramanian, Sreenidhi Mohanvelu, Sheeja Aravindan, Afsana Parveen Jahir Hussain, Sivasubramani Narayanan, Sabir Salim, Loganayaki Periyasamy, Natarajan Aravindan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

8 authors.

Poorvi SubramanianDepartment of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, USA.
Sreenidhi MohanveluDepartment of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, USA.
Sheeja AravindanOU Health Stephenson Cancer Center, Oklahoma City, Oklahoma, USA.
Afsana Parveen Jahir HussainDepartment of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, USA.
Sivasubramani NarayananDepartment of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, USA.
Sabir SalimDepartment of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, USA.
Loganayaki PeriyasamyDepartment of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, USA.
Natarajan AravindanDepartment of Physiological Sciences, Oklahoma State University, Stillwater, Oklahoma, USA.ORCID https://orcid.org/0000-0001-9150-3911

Funding

TUMOR RESISTANCE MECHANISMS TO ANTI-VEGF THERAPY IN PROSTATE CANCER (Sukyung Woo)P20GM103639 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI DHANASEKARAN, DANNY N. · 2012 to 2022
$21.3M
Kerr Foundation 28-34200National Cancer Institute Cancer Center P30CA225520NIH HHS P20GM103639Oklahoma Center for the Advancement of Science and Technology OCAST-HR19-045Oklahoma Tobacco Settlement Endowment Trust R23-03U.S. Department of Defense CA-210339
6 · The paper itself

Abstract

Therapy-resistant neuroblastoma (NB) reflects a lethal convergence of cellular plasticity and immune escape, yet the molecular drivers remain elusive. Here, we identify retinal degeneration protein 3 (RD3) as a master regulator of NB lineage fidelity and tumor immunogenicity. RD3 loss, induced by therapy, triggers a reprogramming cascade involving epithelial-mesenchymal transition, pluripotency circuitry, and cancer stem cell enrichment. Mechanistically, RD3 binds to and regulates the promoter activity of SOX2, NANOG, and OCT3/4, as well as regulates the transcription of EMT factors. Concurrently, RD3 deficiency disrupts antigen presentation (MHC I/II, β2M), upregulates immune checkpoints (PDL1, CD276), and activates immune-suppressive signaling (CD24, CD73, A2AR), fostering an immune-silent microenvironment. RD3 restoration reverses these transitions, reinstating epithelial identity, differentiation, and immune surveillance. In-vivo, RD3 modulates immune cell infiltration, activation, and tumor clearance. Mechanistically, RD3 governs a self-reinforcing axis of cellular identity and immunoediting (by regulating T-cell cytokine release, activation, and cytotoxic function), positioning it as a critical checkpoint in NB evolution. These findings establish RD3 as a dual-function molecular switch and nominate RD3-targeted strategies to re-sensitize high-risk NB to immunotherapy.

Indexed as

Cell PlasticityNeuroblastomaAnimalsEpithelial-Mesenchymal TransitionHumansMiceNeoplastic Stem CellsTumor Microenvironmentcancer immunoeditingcellular plasticityEMTneuroblastomaphenotypic switchingRD3tumor immune evasion

Identifiers

PMID41619263
PMCPMC13067867

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.