Evidence map›Paper›PMID 39402030›Full record

ArticleNature communications2024

A machine learning model reveals expansive downregulation of ligand-receptor interactions that enhance lymphocyte infiltration in melanoma with developed resistance to immune checkpoint blockade.

Sahil Sahni, Binbin Wang, Di Wu, Saugato Rahman Dhruba, Matthew Nagy, Sushant Patkar, Ingrid Ferreira, Chi-Ping Day, Kun Wang, Eytan Ruppin

Abstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing 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

16 citing papers in PubMed.

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  15. Stratified analysis identifies HIF-2bioRxiv : the preprint server for biology · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Sahil SahniCancer Data Science Laboratory (CDSL), Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.ORCID 0009-0006-4678-3903
Binbin WangCancer Data Science Laboratory (CDSL), Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Di WuLaboratory of Pathology, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Saugato Rahman DhrubaCancer Data Science Laboratory (CDSL), Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.ORCID 0000-0001-5947-6757
Matthew NagyCancer Data Science Laboratory (CDSL), Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Sushant PatkarArtificial Intelligence Resource, Molecular Imaging Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.ORCID 0000-0002-5877-0599
Ingrid FerreiraExperimental Cancer Genetics, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.ORCID 0000-0002-4321-5250
Chi-Ping DayCancer Data Science Laboratory (CDSL), Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Kun WangCancer Data Science Laboratory (CDSL), Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA. kwang222@illinois.edu.ORCID 0000-0001-8923-8557
Eytan RuppinCancer Data Science Laboratory (CDSL), Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA. eytan.ruppin@nih.gov.ORCID 0000-0002-7862-3940

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Immune checkpoint blockade (ICB) is a promising cancer therapy; however, resistance frequently develops. To explore ICB resistance mechanisms, we develop Immunotherapy Resistance cell-cell Interaction Scanner (IRIS), a machine learning model aimed at identifying cell-type-specific tumor microenvironment ligand-receptor interactions relevant to ICB resistance. Applying IRIS to deconvolved transcriptomics data of the five largest melanoma ICB cohorts, we identify specific downregulated interactions, termed resistance downregulated interactions (RDI), as tumors develop resistance. These RDIs often involve chemokine signaling and offer a stronger predictive signal for ICB response compared to upregulated interactions or the state-of-the-art published transcriptomics biomarkers. Validation across multiple independent melanoma patient cohorts and modalities confirms that RDI activity is associated with CD8 + T cell infiltration and highly manifested in hot/brisk tumors. This study presents a strongly predictive ICB response biomarker, highlighting the key role of downregulating chemotaxis-associated ligand-receptor interactions in inhibiting lymphocyte infiltration in resistant tumors.

Indexed as

Down-RegulationDrug Resistance, NeoplasmImmune Checkpoint InhibitorsLymphocytes, Tumor-InfiltratingMachine LearningMelanomaTumor MicroenvironmentCD8-Positive T-LymphocytesGene Expression Regulation, NeoplasticHumansImmunotherapyLigandsImmune Checkpoint InhibitorsLigands

Identifiers

PMID39402030
PMCPMC11473774

What OpenQuestion holds

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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.