Evidence map›Paper›PMID 27853827›Full record

ArticleCancer immunology, immunotherapy : CII2017

Increased PD-L1 and T-cell infiltration in the presence of HLA class I expression in metastatic high-grade osteosarcoma: a rationale for T-cell-based immunotherapy.

Yayan T Sundara, Marie Kostine, Arjen H G Cleven, Judith V M G Bovée, Marco W Schilham, Anne-Marie Cleton-Jansen

Open access · hybridAbstract read
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 2 pooled it
5.4field-weighted citation impact, top 3% of its field
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

69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 105 citations in OpenAlex.

  1. Pooled it
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  5. Correlative Analyses of the SARC028 Trial Reveal an Association Between Sarcoma-Associated Immune Infiltrate and Response to Pembrolizumab.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Trial
  6. Article
  7. Review
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  9. Etoposide activates CD8Journal for immunotherapy of cancer · 2025
    Article
  10. A review of immunotherapy for bone tumors.Frontiers in immunology · 2025
    Review
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  12. Review
  13. Review
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  16. Article
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9 more citing papers are in PubMed but not listed here.

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

6 authors at 1 institution in 2 countries.

Yayan T SundaraDepartment of Pathology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Marie KostineDepartment of Pathology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Arjen H G ClevenDepartment of Pathology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Judith V M G BovéeDepartment of Pathology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Marco W SchilhamDepartment of Pediatrics, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Anne-Marie Cleton-JansenDepartment of Pathology, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. a.m.cleton-jansen@lumc.nl.ORCID 0000-0002-9048-4867
Leiden University Medical Center · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionImmunotherapy may be an excellent choice for treating osteosarcoma given its exceptionally high genomic instability, potentially generating neoantigens. In this study, we aim to investigate the HLA class I expression, PD-L1 and tumour-infiltrating lymphocytes in primary osteosarcomas and relapses/metastases, as well as their changes during disease progression. MATERIALS AND

methodsTumour samples from multiple stages of the disease (pretreatment biopsies, surgical resections of primary osteosarcomas, relapses and metastases) were collected and stained for HLA-A (HCA2), HLA-B/C (HC10), β2-microglobulin and PD-L1 using immunohistochemistry on whole sections. Density and type of T-cell infiltrate were characterised by a triple immunofluorescent staining CD3-CD8-FOXP3.

resultsOverall, 85 formalin-fixed, paraffin-embedded blocks from 25 osteosarcoma patients were included. HLA class I expression was detected in 94% of osteosarcomas (strongly positive in 56%, heterogeneous in 38%) and negative or weakly positive in 6%, without differences between the stages of the disease. HLA-A expression was more frequently negative than HLA-B/C. Tumour-infiltrating lymphocytes were highly heterogeneous and mainly observed in tumour areas with expression of HLA class I. Density of T cells was significantly higher in metastases than in primary tumours and local relapses (p = 0.0003). Positive PD-L1 expression was found in 13% of primary tumours, 25% of relapses and 48% of metastases and correlated with a high T-cell infiltrate (p = 0.002).

conclusionAn increased number of tumour-infiltrating T cells and PD-L1 expression in metastases compared with primary tumours, suggesting accessibility for T cells, could imply that osteosarcoma patients with metastatic disease may benefit from T-cell-based immunotherapy.

Indexed as

AdolescentAdultAgedB7-H1 AntigenBiomarkers, TumorBone NeoplasmsChildFemaleHistocompatibility Antigens Class IHumansImmunotherapyLymphocytes, Tumor-InfiltratingMaleMiddle AgedNeoplasm MetastasisOsteosarcomaB7-H1 AntigenBiomarkers, TumorCD274 protein, humanHistocompatibility Antigens Class IHLA class IImmunotherapyOsteosarcomaPD-L1Tumour-infiltrating lymphocytes

Identifiers

PMID27853827
PMCPMC5222929
OpenAlexW2553835169

What OpenQuestion holds

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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.