Evidence mapPaperPMID 41953014Full record

ReviewFrontiers in immunology2026

Immune exclusion as a recurrent immune-escape state driving treatment resistance in osteosarcoma: insights from single-cell, spatial, and multi-omics studies.

Yunxia Zeng, Yiyao Xiang, Lang Chen, Yuan Wen, Changjie Deng, Xinyu Huang, Lei Feng, Shili Liu, Heng Zhao

Abstract readReview
In one paragraph

Review in Frontiers in immunology, 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. Article
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

9 authors.

Yunxia Zeng *Department of Orthopaedics, The Fourth Affiliated Hospital of Southwest Medical University, Meishan, China.
Yiyao Xiang *Department of Orthopaedics, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Lang Chen *Department of Emergency Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Yuan WenHealth Management Center, The Fourth Affiliated Hospital of Southwest Medical University, Meishan, China.
Changjie DengDepartment of Medical Equipment, The Fourth Affiliated Hospital of Southwest Medical University, Meishan, China.
Xinyu HuangDepartment of Medical Equipment, The Fourth Affiliated Hospital of Southwest Medical University, Meishan, China.
Lei FengIntensive Care Unit, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Shili LiuIntensive Care Unit, The Fourth Affiliated Hospital of Southwest Medical University, Meishan, China.
Heng ZhaoDepartment of Orthopaedics, The Fourth Affiliated Hospital of Southwest Medical University, Meishan, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osteosarcoma remains a therapeutically challenging malignancy with durable responses limited by frequent treatment resistance. Although immune activity is detectable in many tumors, immunotherapy and combination strategies show limited clinical benefit, indicating immune dysfunction extends beyond tumor-intrinsic mechanisms. Growing evidence identifies immune exclusion as a key immunological barrier in osteosarcoma, characterized by spatial and functional segregation of immune cells from malignant areas despite their presence in the tumor microenvironment. Here, we use immune exclusion as a working term to describe contexts in which immune cells are present but have limited effective access to, or engagement with, malignant cells-distinct from immune desert (near-absence of infiltrates) and immune-cold states (weak effector activation despite some infiltration). In this mini-review, we focus on immune exclusion as a context-dependent immunological driver of treatment resistance in osteosarcoma. We integrate insights from single-cell sequencing, spatial profiling, and multi-omics studies to characterize the immunological features of immune exclusion, highlight bone-associated structural and regulatory factors, and explore how exclusion creates selective pressure leading to therapeutic failure. Emerging data indicate that immune exclusion represents a coordinated program involving tumor, stromal, and immune elements, resulting in impaired immune-tumor interaction and ineffective clearance. We discuss the translational implications, stressing immune-context modulation as essential for re-sensitization and noting that many current single-cell and spatial datasets remain limited in sample size, sampling sites, and treatment background. Framing resistance through immune exclusion offers an immune-centric framework for understanding and overcoming treatment resistance in osteosarcoma.

Indexed as

Bone NeoplasmsDrug Resistance, NeoplasmOsteosarcomaTumor EscapeAnimalsHumansMultiomicsSingle-Cell AnalysisTumor Microenvironmentimmune exclusionmulti-omics integrationosteosarcomasingle-cell sequencingtreatment resistancetumor immune microenvironment

Identifiers

PMID41953014
PMCPMC13055542

What Socratic 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 Socratic graph.