Evidence map›Paper›PMID 33736924›Full record

ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2021

High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types.

D J McGrail, P G Pilié, N U Rashid, L Voorwerk, M Slagter, M Kok, E Jonasch, M Khasraw, A B Heimberger, B Lim and 6 more

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

Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 671 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
671citing papers in PubMed, 2 pooled it
77.5field-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.

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

671 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,029 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  6. TAPISTRY: A Phase II Study of Atezolizumab in Patients with Tumor Mutational Burden-High Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
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  9. Observational
  10. Review
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  12. Article
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  16. Image-based PD-L1 scoring and tumor-infiltrating lymphocytes as predictors for the response to neoadjuvant chemoimmunotherapy in non-small cell lung cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
  17. Article
  18. Genetic insights into lung squamous cell carcinoma: howTranslational cancer research · 2026
    Article
  19. Article
  20. Article

611 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 5 institutions in 2 countries.

D J McGrailDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: djmcgrail@mdanderson.org.
P G PiliéDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
N U RashidLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, USA; Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, USA.
L VoorwerkDivision of Tumor Biology & Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
M SlagterDivision of Molecular Oncology & Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Oncode Institute, Utrecht, The Netherlands.
M KokDivision of Tumor Biology & Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
E JonaschDepartment of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
M KhasrawThe Preston Robert Tisch Brain Tumor Center, Duke University, Durham, USA.
A B HeimbergerDepartment of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, USA.
B LimDepartment of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
N T UenoDepartment of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
J K LittonDepartment of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
R FerrarottoDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
J T ChangDepartment of Integrative Biology and Pharmacology, The University of Texas Health Sciences Center at Houston, Houston, USA; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, USA.
S L MoulderDepartment of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
S-Y LinDepartment of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: sylin@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USOncode Institute · NLDuke University · USThe Netherlands Cancer Institute · NLUniversity of North Carolina at Chapel Hill · US

Funding

Signature-guided therapy for mismatch repair defective cancersR01CA218287 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LIN, SHIAW-YIH · 2017 to 2021
$1.9M
Determining the Immunological Consequences of DNA Replication Stress Response Defects in Renal Cells Carcinoma to Improve Immunotherapy OutcomesK99CA240689 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MCGRAIL, DANIEL JAMES · 2019 to 2020
$207k
NCI NIH HHS K99 CA240689NCI NIH HHS R01 CA218287
6 · The paper itself

Abstract

backgroundHigh tumor mutation burden (TMB-H) has been proposed as a predictive biomarker for response to immune checkpoint blockade (ICB), largely due to the potential for tumor mutations to generate immunogenic neoantigens. Despite recent pan-cancer approval of ICB treatment for any TMB-H tumor, as assessed by the targeted FoundationOne CDx assay in nine tumor types, the utility of this biomarker has not been fully demonstrated across all cancers. PATIENTS AND

methodsData from over 10 000 patient tumors included in The Cancer Genome Atlas were used to compare approaches to determine TMB and identify the correlation between predicted neoantigen load and CD8 T cells. Association of TMB with ICB treatment outcomes was analyzed by both objective response rates (ORRs, N = 1551) and overall survival (OS, N = 1936).

resultsIn cancer types where CD8 T-cell levels positively correlated with neoantigen load, such as melanoma, lung, and bladder cancers, TMB-H tumors exhibited a 39.8% ORR to ICB [95% confidence interval (CI) 34.9-44.8], which was significantly higher than that observed in low TMB (TMB-L) tumors [odds ratio (OR) = 4.1, 95% CI 2.9-5.8, P < 2 × 10

conclusionsOur analysis failed to support application of TMB-H as a biomarker for treatment with ICB in all solid cancer types. Further tumor type-specific studies are warranted.

Indexed as

Immune Checkpoint InhibitorsNeoplasmsBiomarkers, TumorHumansMaleMutationTreatment OutcomeBiomarkers, TumorImmune Checkpoint Inhibitorsbiomarkerimmune checkpoint blockadetumor mutation burden

Identifiers

PMID33736924
PMCPMC8053682
OpenAlexW3136653115

What OpenQuestion holds

Textmetadata
LicenceTDM
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.