Evidence map›Paper›PMID 36096531›Full record

ArticleJournal for immunotherapy of cancer2022

Unveiling the tumor immune microenvironment of organ-specific melanoma metastatic sites.

Jordan W Conway, Robert V Rawson, Serigne Lo, Tasnia Ahmed, Ismael A Vergara, Tuba N Gide, Grace Heloise Attrill, Matteo S Carlino, Robyn P M Saw, John F Thompson and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
5.1field-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

41 citing papers in PubMed, 55 citations in OpenAlex.

  1. Exploring uncertainties in melanoma management: a Spanish multidisciplinary Delphi consensus.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
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  18. [18F]-FDG PET-CT in Malignant Melanoma.Diagnostics (Basel, Switzerland) · 2025
    Article
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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

18 authors at 1 institution in 1 country.

Jordan W ConwayMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.ORCID 0000-0003-1161-9119
Robert V RawsonMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Serigne LoMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.ORCID 0000-0001-5092-5544
Tasnia AhmedMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Ismael A VergaraMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Tuba N GideMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Grace Heloise AttrillMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.ORCID 0000-0001-8926-6582
Matteo S CarlinoMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Robyn P M SawMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
John F ThompsonMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.ORCID 0000-0002-2816-2496
Andrew J SpillaneMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Kerwin F ShannonMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Brindha ShivalingamMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Alexander Maxwell MenziesMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
James S WilmottMelanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.
Georgina V Long *Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.ORCID 0000-0001-8894-3545
Richard A Scolyer *Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia.ORCID 0000-0002-8991-0013
Ines Pires da Silva *Melanoma Institute Australia, The University of Sydney, Sydney, New South Wales, Australia Ines.Silva@melanoma.org.au.ORCID 0000-0003-3540-8906
The University of Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe liver is a known site of resistance to immunotherapy and the presence of liver metastases is associated with shorter progression-free and overall survival (OS) in melanoma, while lung metastases have been associated with a more favorable outcome. There are limited data available regarding the immune microenvironment at different anatomical sites of melanoma metastases. This study sought to characterize and compare the tumor immune microenvironment of liver, brain, lung, subcutaneous (subcut) as well as lymph node (LN) melanoma metastases.

methodsWe analyzed OS in 1924 systemic treatment-naïve patients with AJCC (American Joint Committee on Cancer) stage IV melanoma with a solitary site of organ metastasis. In an independent cohort we analyzed and compared immune cell densities, subpopulations and spatial distribution in tissue from liver, lung, brain, LN or subcut sites from 130 patients with stage IV melanoma.

resultsPatients with only liver, brain or bone metastases had shorter OS compared to those with lung, LN or subcutaneous and soft tissue metastases. Liver and brain metastases had significantly lower T-cell infiltration than lung (p=0.0116 and p=0.0252, respectively) and LN metastases (p=0.0116 and p=0.0252, respectively). T cells were further away from melanoma cells in liver than lung metastases (p=0.0335). Liver metastases displayed unique T-cell profiles, with a significantly lower proportion of programmed cell death protein-1+ T cells compared to all other anatomical sites (p<0.05), and a higher proportion of TIM-3+ T cells compared to LN (p=0.0004), subcut (p=0.0082) and brain (p=0.0128) metastases. Brain metastases had a lower macrophage density than subcut (p=0.0105), liver (p=0.0095) and lung (p<0.0001) metastases. Lung metastases had the highest proportion of programmed death ligand-1+ macrophages of the total macrophage population, significantly higher than brain (p<0.0001) and liver metastases (p=0.0392).

conclusionsLiver and brain melanoma metastases have a significantly reduced immune infiltrate than lung, subcut and LN metastases, which may account for poorer prognosis and reduced immunotherapy response rates in patients with liver or brain metastases. Increased TIM-3 expression in liver metastases suggests TIM-3 inhibitor therapy as a potential therapeutic opportunity to improve patient outcomes.

Indexed as

Brain NeoplasmsLiver NeoplasmsLung NeoplasmsMelanomaHepatitis A Virus Cellular Receptor 2HumansLymphatic MetastasisTumor MicroenvironmentHAVCR2 protein, humanHepatitis A Virus Cellular Receptor 2ImmunohistochemistryMacrophagesMelanomaT-LymphocytesTumor Microenvironment

Identifiers

PMID36096531
PMCPMC9472156
OpenAlexW4295484467

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.