Evidence map›Paper›PMID 34446728›Full record

Trial reportNature communications2021

Pan-cancer analysis of longitudinal metastatic tumors reveals genomic alterations and immune landscape dynamics associated with pembrolizumab sensitivity.

S Y Cindy Yang, Scott C Lien, Ben X Wang, Derek L Clouthier, Youstina Hanna, Iulia Cirlan, Kelsey Zhu, Jeffrey P Bruce, Samah El Ghamrasni, Marco A J Iafolla and 17 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02644369 (Investigator-initiated Phase II Study of Pembrolizumab Immunological Response Evaluation), which is not on this map. Cited by 67 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 1 pooled it
9.3field-weighted citation impact, top 1% 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.

NCT02644369 phase2active not recruitingnot on this map

Investigator-initiated Phase II Study of Pembrolizumab Immunological Response Evaluation

TypeinterventionalSponsorUniversity Health Network, TorontoRan2016 to 2026Enrolled100ConditionsSquamous Cell Cancer of Head and Neck, Triple Negative Breast Cancer, Epithelial Ovarian Cancer, Malignant MelanomaArmsPembrolizumab
3 · Its place in the literature

Who cites it

67 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.

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  14. Interferon Epsilon Loss Is Elusive 9p21 Link to Immune-Cold Tumors, Resistant to Immune Checkpoint Therapy, and Endogenous CXCL9/10 Induction.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2025
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7 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

27 authors at 4 institutions in 2 countries.

S Y Cindy YangDepartment of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Scott C LienDepartment of Immunology, University of Toronto, Toronto, ON, Canada.
Ben X WangPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Derek L ClouthierPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Youstina HannaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Iulia CirlanPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Kelsey ZhuPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Jeffrey P BrucePrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Samah El GhamrasniPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0003-4346-1360
Marco A J IafollaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Marc OlivaPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0001-5352-8130
Aaron R HansenPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Anna SpreaficoPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Philippe L BedardPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0002-6771-2999
Stephanie LheureuxPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Albiruni RazakPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Vanessa SpeersPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Hal K BermanPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.ORCID 0000-0001-7524-7911
Alexey AleshinNatera, Inc., San Carlos, CA, USA.
Benjamin Haibe-KainsDepartment of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
David G BrooksDepartment of Immunology, University of Toronto, Toronto, ON, Canada.
Tracy L McGahaDepartment of Immunology, University of Toronto, Toronto, ON, Canada.ORCID 0000-0003-4721-9301
Marcus O ButlerDepartment of Immunology, University of Toronto, Toronto, ON, Canada.ORCID 0000-0002-9840-7057
Scott V BratmanDepartment of Medical Biophysics, University of Toronto, Toronto, ON, Canada.ORCID 0000-0001-8610-4908
Pamela S OhashiDepartment of Immunology, University of Toronto, Toronto, ON, Canada.
Lillian L SiuPrincess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada. lillian.siu@uhn.ca.ORCID 0000-0002-3500-0540
Trevor J PughDepartment of Medical Biophysics, University of Toronto, Toronto, ON, Canada. trevor.pugh@utoronto.ca.ORCID 0000-0002-8073-5888
University Health Network · CAOntario Institute for Cancer Research · CAUniversity of Toronto · CANatera (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Serial circulating tumor DNA (ctDNA) monitoring is emerging as a non-invasive strategy to predict and monitor immune checkpoint blockade (ICB) therapeutic efficacy across cancer types. Yet, limited data exist to show the relationship between ctDNA dynamics and tumor genome and immune microenvironment in patients receiving ICB. Here, we present an in-depth analysis of clinical, whole-exome, transcriptome, and ctDNA profiles of 73 patients with advanced solid tumors, across 30 cancer types, from a phase II basket clinical trial of pembrolizumab (NCT02644369) and report changes in genomic and immune landscapes (primary outcomes). Patients stratified by ctDNA and tumor burden dynamics correspond with survival and clinical benefit. High mutation burden, high expression of immune signatures, and mutations in BRCA2 are associated with pembrolizumab molecular sensitivity, while abundant copy-number alterations and B2M loss-of-heterozygosity corresponded with resistance. Upon treatment, induction of genes expressed by T cell, B cell, and myeloid cell populations are consistent with sensitivity and resistance. We identified the upregulated expression of PLA2G2D, an immune-regulating phospholipase, as a potential biomarker of adaptive resistance to ICB. Together, these findings provide insights into the diversity of immunogenomic mechanisms that underpin pembrolizumab outcomes.

Indexed as

Antibodies, Monoclonal, HumanizedAntineoplastic AgentsBRCA2 ProteinCirculating Tumor DNADNA Copy Number VariationsDrug Resistance, NeoplasmExome SequencingGroup II Phospholipases A2HumansNeoplasmsProspective StudiesTumor BurdenTumor EscapeAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBRCA2 ProteinBRCA2 protein, humanCirculating Tumor DNAGroup II Phospholipases A2pembrolizumabPLA2G2D protein, human

Identifiers

PMID34446728
PMCPMC8390680
OpenAlexW3196194192

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.