Evidence map›Paper›PMID 41567220›Full record

ReviewFrontiers in immunology2025

Neurotrophin NGF/TrkA and BDNF/TrkB signaling orchestrates the immune microenvironment in osteosarcoma.

Hongyuan Liu, Guobing Wang, Chunxue Wang, Dan Hou, Shigang Li, Yuansheng Fan, Bing Liu

Abstract readReview
In one paragraph

Review in Frontiers in immunology, 2025. 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

7 authors.

Hongyuan LiuOrthopedics and Traumatology Department, Yibin Traditional Chinese Medicine Hospital, Yibin, China.
Guobing WangMedical Research Laboratory, Yibin Traditional Chinese Medicine Hospital, Yibin, China.
Chunxue WangOutpatient, Yibin Traditional Chinese Medicine Hospital, Yibin, China.
Dan HouOrthopedics and Traumatology Department, Yibin Traditional Chinese Medicine Hospital, Yibin, China.
Shigang LiOrthopedics and Traumatology Department, Yibin Traditional Chinese Medicine Hospital, Yibin, China.
Yuansheng FanOrthopedics and Traumatology Department, Yibin Traditional Chinese Medicine Hospital, Yibin, China.
Bing LiuOrthopedics and Traumatology Department, Yibin Traditional Chinese Medicine Hospital, Yibin, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Neurotrophin signaling through NGF/TrkA and BDNF/TrkB is increasingly recognized as a driver of osteosarcoma (OS) progression and an organizer of its immune milieu, yet clinical translation has lagged amid intratumoral heterogeneity and a myeloid-skewed, vasculature-aberrant tumor microenvironment (TME). Features that blunt immune competence include dominant tumor-associated macrophage programs, sparse and dysfunctional effector T cells, endothelial remodeling that restricts lymphocyte entry, and neuron-immune circuits that reinforce suppression. Within this context, NGF/TrkA promotes matrix remodeling, monocyte ingress, and macrophage polarization, while BDNF/TrkB modulates dendritic-cell maturation, supports survival and angiogenesis, and may condition T-cell priming-together positioning neurotrophins as coordinators of tumor persistence and immune exclusion. This review surveys these mechanisms and maps them to therapeutic strategies: kinase-level blockade with approved TRK inhibitors in NTRK fusion-positive disease; exploratory pathway inhibition in fusion-negative OS; ligand-directed approaches; and rational combinations with immunotherapy and vascular/stromal modulators. We highlight biomarker frameworks (receptor-ligand activity scores, phospho-Trk immunohistochemistry, NGF-MMP-2 readouts) and safety considerations that should structure early-phase trials. Clinical and preclinical signals collectively support testing neurotrophin-targeted strategies to recalibrate myeloid composition, enhance antigen presentation, and restore T-cell access to tumor beds. The purpose of this review is to synthesize current evidence and propose a translational roadmap for targeting NGF/TrkA and BDNF/TrkB to remodel antitumor immunity in osteosarcoma.

Indexed as

Bone NeoplasmsBrain-Derived Neurotrophic FactorMembrane GlycoproteinsNerve Growth FactorOsteosarcomaReceptor, trkAReceptor, trkBSignal TransductionTumor MicroenvironmentAnimalsHumansBDNF protein, humanBrain-Derived Neurotrophic FactorMembrane GlycoproteinsNerve Growth FactorNTRK1 protein, humanReceptor, trkAReceptor, trkBtropomyosin-related kinase-B, humanantitumor immunitydendritic cellsmyeloid polarizationneurotrophinsosteosarcomatumor-associated macrophages

Identifiers

PMID41567220
PMCPMC12816227

What Socratic 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 Socratic graph.