Evidence map›Paper›PMID 24129241›Full record

ArticleBritish journal of cancer2013

CXCR3/CCR5 pathways in metastatic melanoma patients treated with adoptive therapy and interleukin-2.

D Bedognetti, T L Spivey, Y Zhao, L Uccellini, S Tomei, M E Dudley, M L Ascierto, V De Giorgi, Q Liu, L G Delogu and 6 more

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

Article in British journal of cancer, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

83 citing papers in PubMed, 150 citations in OpenAlex.

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  18. The immune landscape of solid pediatric tumors.Journal of experimental & clinical cancer research : CR · 2022
    Article
  19. Overview of Research on Germline Genetic Variation in Immune Genes and Cancer Outcomes.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2022
    Article
  20. Review

23 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

16 authors at 8 institutions in 3 countries.

D Bedognetti1] Infectious Disease and Immunogenetics Section (IDIS), Department of Transfusion Medicine, Clinical Center and trans-NIH Center for Human Immunology (CHI), National Institutes of Health, Bethesda, MD 20892, USA [2] Department of Oncology, Biology, Genetics (DOBIG), University of Genoa and National Cancer Research Institute, 16132 Genoa, Italy [3] Department of Internal Medicine (DiMI), University of Genoa, 16132 Genoa, Italy.
T L Spivey
Y Zhao
L Uccellini
S Tomei
M E Dudley
M L Ascierto
V De Giorgi
Q Liu
L G Delogu
M Sommariva
M R Sertoli
R Simon
E Wang
S A Rosenberg
F M Marincola
National Institutes of Health Clinical Center · USNational Cancer Institute · USNational Institutes of Health · USUniversity of Genoa · ITRush University Medical Center · USSidra Medical and Research Center · QAUniversity of Milan · ITUniversity of Sassari · IT

Funding

Intramural NIH HHS
6 · The paper itself

Abstract

backgroundAdoptive therapy with tumour-infiltrating lymphocytes (TILs) induces durable complete responses (CR) in ∼20% of patients with metastatic melanoma. The recruitment of T cells through CXCR3/CCR5 chemokine ligands is critical for immune-mediated rejection. We postulated that polymorphisms and/or expression of CXCR3/CCR5 in TILs and the expression of their ligands in tumour influence the migration of TILs to tumours and tumour regression.

methodsTumour-infiltrating lymphocytes from 142 metastatic melanoma patients enrolled in adoptive therapy trials were genotyped for CXCR3 rs2280964 and CCR5-Δ32 deletion, which encodes a protein not expressed on the cell surface. Expression of CXCR3/CCR5 in TILs and CXCR3/CCR5 and ligand genes in 113 available parental tumours was also assessed. Tumour-infiltrating lymphocyte data were validated by flow cytometry (N=50).

resultsThe full gene expression/polymorphism model, which includes CXCR3 and CCR5 expression data, CCR5-Δ32 polymorphism data and their interaction, was significantly associated with both CR and overall response (OR; P=0.0009, and P=0.007, respectively). More in detail, the predicted underexpression of both CXCR3 and CCR5 according to gene expression and polymorphism data (protein prediction model, PPM) was associated with response to therapy (odds ratio=6.16 and 2.32, for CR and OR, respectively). Flow cytometric analysis confirmed the PPM. Coordinate upregulation of CXCL9, CXCL10, CXCL11, and CCL5 in pretreatment tumour biopsies was associated with OR.

conclusionCoordinate overexpression of CXCL9, CXCL10, CXCL11, and CCL5 in pretreatment tumours was associated with responsiveness to treatment. Conversely, CCR5-Δ32 polymorphism and CXCR3/CCR5 underexpression influence downregulation of the corresponding receptors in TILs and were associated with likelihood and degree of response.

Indexed as

AdolescentAdultAgedBiopsyCell MovementFemaleGene ExpressionGenotypeHumansInterleukin-2LigandsLymphocytes, Tumor-InfiltratingMaleMelanomaMiddle AgedPolymorphism, GeneticCCR5 protein, humanCXCR3 protein, humanInterleukin-2LigandsReceptors, CCR5Receptors, CXCR3

Identifiers

PMID24129241
PMCPMC3817317
OpenAlexW1990270625

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.