Evidence map›Paper›PMID 27913861›Full record

ArticleVirchows Archiv : an international journal of pathology2017

CXCL12 expression and PD-L1 expression serve as prognostic biomarkers in HCC and are induced by hypoxia.

Alexander Semaan, Dimo Dietrich, Dominik Bergheim, Jörn Dietrich, Jörg C Kalff, Vittorio Branchi, Hanno Matthaei, Glen Kristiansen, Hans-Peter Fischer, Diane Goltz

Abstract read
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In one paragraph

Article in Virchows Archiv : an international journal of pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 3 pooled it
4.1field-weighted citation impact, top 5% 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

49 citing papers in PubMed, 3 syntheses or guidelines pooled it, 74 citations in OpenAlex.

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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

10 authors at 1 institution in 1 country.

Alexander SemaanDepartment of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Bonn, Germany.
Dimo DietrichDepartment of Otolaryngology, Head and Neck Surgery, University of Bonn, Bonn, Germany.
Dominik BergheimInstitute of Pathology, University of Bonn, Sigmund Freud Str. 25, 53105, Bonn, Germany.
Jörn DietrichDepartment of Otolaryngology, Head and Neck Surgery, University of Bonn, Bonn, Germany.
Jörg C KalffDepartment of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Bonn, Germany.
Vittorio BranchiDepartment of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Bonn, Germany.
Hanno MatthaeiDepartment of General, Visceral, Thoracic and Vascular Surgery, University of Bonn, Bonn, Germany.
Glen KristiansenInstitute of Pathology, University of Bonn, Sigmund Freud Str. 25, 53105, Bonn, Germany.
Hans-Peter FischerInstitute of Pathology, University of Bonn, Sigmund Freud Str. 25, 53105, Bonn, Germany.
Diane GoltzInstitute of Pathology, University of Bonn, Sigmund Freud Str. 25, 53105, Bonn, Germany. diane.goltz@uni-bonn.de.
University of Bonn · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Anti-PD-1 treatment increases anti-tumour immune responses in animal models of hepatocellular carcinoma (HCC). Sorafenib, the mainstay of treatment of HCC patients, however, leads to tumour hypoxia and thereby abrogates the efficacy of anti-PD-1 treatment. This served as a rationale to implement CXCR4 inhibition as adjunct to sorafenib and anti-PD-1 treatment in murine HCC models. We studied the relationship between tumour hypoxia, PD-L1 and CXCL12 expression in human HCC, aiming to test the rationale for triple therapy combining sorafenib, PD-1 immune checkpoint inhibitors and CXCR4 inhibitors. Expression of CXCL12, PD-L1 and of surrogate markers for tumour hypoxia was evaluated at messenger RNA (mRNA) level in a cohort of HCC patients from The Cancer Genome Atlas and immunohistochemically in an independent cohort from the University Hospital of Bonn. Retrospective survival analyses were conducted. CXCL12 mRNA level significantly correlated with markers indicating tumour hypoxia in HCC (HIF1-α ρ = 0.104, p = 0.047). PD-L1 expression was significantly increased in tumours with a high number of tumour-infiltrating lymphocytes (ρ = 0.533, p < 0.001). In Cox proportional hazard analyses, high PD-L1 expression and loss of nuclear CXCL12 expression showed significant prognostic value in terms of overall survival (hazard ratio (HR) = 3.35 [95%CI 1.33-8.46], p = 0.011 for PD-L1; HR = 2.64 [95%CI 1.18-5.88], p = 0.018 for CXCL12, respectively). This study supports the rationale to combine CXCR4 inhibitors and PD-1 immune checkpoint inhibitors in patients with HCC, as sorafenib-induced tumour hypoxia leads to upregulation of PD-L1 and CXCL12.

Indexed as

AdolescentAdultAgedAged, 80 and overAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorCarcinoma, HepatocellularChemokine CXCL12Chemotherapy, AdjuvantFemaleHepatectomyHumansHypoxiaImmunohistochemistryAntineoplastic AgentsB7-H1 AntigenBiomarkers, TumorCD274 protein, humanChemokine CXCL12CXCL12 protein, humanNiacinamidePhenylurea CompoundsSorafenibCXCL12Hepatocellular carcinomaHypoxiaImmune checkpoint inhibitor PD-L1Tumour-infiltrating lymphocytes

Identifiers

PMID27913861
OpenAlexW2557827074

What OpenQuestion holds

Textmetadata
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.