Evidence map›Paper›PMID 32457125›Full record

ArticleJournal for immunotherapy of cancer2020

In-depth plasma proteomics reveals increase in circulating PD-1 during anti-PD-1 immunotherapy in patients with metastatic cutaneous melanoma.

Haris Babačić, Janne Lehtiö, Yago Pico de Coaña, Maria Pernemalm, Hanna Eriksson

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 2 pooled it
2.6field-weighted citation impact, top 8% 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, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Towards liquid biopsy-based analysis of antitumour immunity.Nature reviews. Clinical oncology · 2026
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  19. Proteomic Investigation of Immune Checkpoints and Some of Their Inhibitors.International journal of molecular sciences · 2024
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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

5 authors at 2 institutions in 1 country.

Haris BabačićDepartment of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.ORCID 0000-0003-0813-0005
Janne LehtiöDepartment of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.
Yago Pico de CoañaDepartment of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.
Maria PernemalmDepartment of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden maria.pernemalm@ki.se.
Hanna ErikssonDepartment of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden.
Karolinska Institutet · SEKarolinska University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundImmune checkpoint inhibitors (ICIs) have significantly improved the outcome in metastatic cutaneous melanoma (CM). However, therapy response is limited to subgroups of patients and clinically useful predictive biomarkers are lacking.

methodsTo discover treatment-related systemic changes in plasma and potential biomarkers associated with treatment outcome, we analyzed serial plasma samples from 24 patients with metastatic CM, collected before and during ICI treatment, with mass-spectrometry-based global proteomics (high-resolution isoelectric focusing liquid chromatography-mass spectrometry (HiRIEF LC-MS/MS)) and targeted proteomics with proximity extension assays (PEAs). In addition, we analyzed plasma proteomes of 24 patients with metastatic CM treated with mitogen-activated protein kinase inhibitors (MAPKis), to pinpoint changes in protein plasma levels specific to the ICI treatment. To detect plasma proteins associated with treatment response, we performed stratified analyses in anti-programmed cell death protein 1 (anti-PD-1) responders and non-responders. In addition, we analyzed the association between protein plasma levels and progression-free survival (PFS) by Cox proportional hazards models.

resultsUnbiased HiRIEF LC-MS/MS-based proteomics showed plasma levels' alterations related to anti-PD-1 treatment in 80 out of 1160 quantified proteins. Circulating PD-1 had the highest increase during anti-PD-1 treatment (log2-FC=2.03, p=0.0008) and in anti-PD-1 responders (log2-FC=2.09, p=0.005), but did not change in the MAPKis cohort. Targeted, antibody-based proteomics by PEA confirmed this observation. Anti-PD-1 responders had an increase in plasma proteins involved in T-cell response, neutrophil degranulation, inflammation, cell adhesion, and immune suppression. Furthermore, we discovered new associations between plasma proteins (eg, interleukin 6, interleukin 10, proline-rich acidic protein 1, desmocollin 3, C-C motif chemokine ligands 2, 3 and 4, vascular endothelial growth factor A) and PFS, which may serve as predictive biomarkers.

conclusionsWe detected an increase in circulating PD-1 during anti-PD-1 treatment, as well as diverse immune plasma proteomic signatures in anti-PD-1 responders. This study demonstrates the potential of plasma proteomics as a liquid biopsy method and in discovery of putative predictive biomarkers for anti-PD-1 treatment in metastatic CM.

Indexed as

AgedCutaneous Malignant MelanomaFemaleHumansImmune Checkpoint InhibitorsImmunotherapyMaleMelanomaProgrammed Cell Death 1 ReceptorProteomicsSkin NeoplasmsImmune Checkpoint InhibitorsPDCD1 protein, humanProgrammed Cell Death 1 Receptorimmunotherapymelanomaprogrammed cell death 1 receptortumor biomarkers

Identifiers

PMID32457125
PMCPMC7253007
OpenAlexW3029881542

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.