Evidence map›Paper›PMID 41559679›Full record

ArticleJournal of experimental & clinical cancer research : CR2026

GLUT1 expression, lymphocyte distribution and CD3

Elizabeth C Paver, Tuba N Gide, Zarwa Yaseen, Paola Cornejo-Paramo, Peter Ferguson, Nigel G Maher, Alexander M Menzies, Matteo S Carlino, Ines Pires da Silva, Jeff Holst and 3 more

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In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

13 authors.

Elizabeth C Paver *Melanoma Institute Australia, The University of Sydney, Sydney, Australia.
Tuba N Gide *Melanoma Institute Australia, The University of Sydney, Sydney, Australia. tuba.gide@sydney.edu.au.
Zarwa YaseenMelanoma Institute Australia, The University of Sydney, Sydney, Australia.
Paola Cornejo-ParamoMelanoma Institute Australia, The University of Sydney, Sydney, Australia.
Peter FergusonMelanoma Institute Australia, The University of Sydney, Sydney, Australia.
Nigel G MaherMelanoma Institute Australia, The University of Sydney, Sydney, Australia.
Alexander M MenziesMelanoma Institute Australia, The University of Sydney, Sydney, Australia.
Matteo S CarlinoMelanoma Institute Australia, The University of Sydney, Sydney, Australia.
Ines Pires da SilvaMelanoma Institute Australia, The University of Sydney, Sydney, Australia.
Jeff HolstSchool of Biomedical Sciences, UNSW Sydney, Kensington, Australia.
Georgina V Long *Melanoma Institute Australia, The University of Sydney, Sydney, Australia.
Richard A Scolyer *Melanoma Institute Australia, The University of Sydney, Sydney, Australia.
James S Wilmott *Melanoma Institute Australia, The University of Sydney, Sydney, Australia.

Funding

Cancer Institute NSW ECF1376Cancer Institute NSW TPG 2021/TPG2114National Health and Medical Research Council APP2009476National Health and Medical Research Council GNT2007839National Health and Medical Research Council GNT2018514National Health and Medical Research Council GNT2033462Sydney Cancer Partners and Maridulu Budyari Gumal (SPHERE) Cancer CAG 2021/CBG0002 & 2021/CBG0003
6 · The paper itself

Abstract

backgroundGlycolysis, commonly used by malignant tumors for energy production, results in acidification of the tumor microenvironment (TME) through the secretion and accumulation of lactic acid. Acidosis is a potent inhibitor of immune cell function and may therefore affect T-cell infiltration and the efficacy of immunotherapy. This study aimed to characterize the metabolic tumor microenvironment and its association with lymphocyte distribution in patients with advanced melanoma treated with immune checkpoint blockade (ICB) therapies.

methodsPre-treatment formalin-fixed, paraffin-embedded metastatic melanoma specimens from 45 patients treated with anti-PD-1 ± anti-CTLA-4 ICB were included in this study. Patients with progression-free survival (PFS) ≥ 6mo were categorized as responders (n = 23), while non-responders had a PFS < 6mo (n = 22). Two custom multiplex immunofluorescence panels were developed to evaluate the expression and distribution of markers of a hypoxic microenvironment (CA9 and HIF1α), glycolysis (GLUT1 and GLUT3) and vessels (CD31) in relation to melanocytes (SOX10) and T lymphocytes (CD3).

resultsGLUT1 + melanoma regions contained significantly lower proportions of CD3+ T-cells than GLUT1- regions (p < 0.0001). Responders displayed significantly higher proportions of intratumoral T-cells expressing GLUT1 (p = 0.049) and GLUT3 (p = 0.043) compared to non-responders. CD3+ T-cells co-expressing hypoxia-associated markers were present in higher proportions significantly closer to GLUT1+ melanoma cells in responders compared to non-responders (p < 0.05). Patients with higher proportions of CD3+ T-cells and CD3+CA9+ T-cells within the 20 µm distance to GLUT1+ melanoma cells had significantly longer progression-free survival (p = 0.0133 and p = 0.0378, respectively).

conclusionsTogether, these findings support the hypothesis that the presence of glycolysis in melanoma (as inferred by increased GLUT expression) may affect the ability of T-cells to infiltrate tumors and function effectively. The results also suggest that the overall proportion and spatial distribution of GLUT+ T-cells, including those displaying evidence of adaptation to a hypoxic/acidic TME, may be relevant for responses to ICB therapy.

Indexed as

CD3 ComplexGlucose Transporter Type 1ImmunotherapyMelanomaT-Lymphocyte SubsetsAdultAgedBiomarkers, TumorFemaleHumansLymphocytes, Tumor-InfiltratingMaleMiddle AgedTumor MicroenvironmentBiomarkers, TumorCD3 ComplexGlucose Transporter Type 1SLC2A1 protein, humanGLUT1GLUT3ImmunotherapyMelanomaMetabolic tumor microenvironmentMultiplex immunofluorescenceSpatial distributionTumor-infiltrating lymphocytes

Identifiers

PMID41559679
PMCPMC12903248

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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.