Evidence map›Paper›PMID 35973335›Full record

ArticleLung cancer (Amsterdam, Netherlands)2022

Immunogenomic profiling of lung adenocarcinoma reveals poorly differentiated tumors are associated with an immunogenic tumor microenvironment.

Neal Akhave, Jiexin Zhang, Erin Bayley, Meredith Frank, Shin-Heng Chiou, Carmen Behrens, Runzhe Chen, Xin Hu, Edwin Roger Parra, Won-Chul Lee and 17 more

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

Article in Lung cancer (Amsterdam, Netherlands), 2022. 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
1.8field-weighted citation impact, top 14% 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

16 citing papers in PubMed, 20 citations in OpenAlex.

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  13. Micropapillary and Solid Histologic Patterns in N1 and N2 Lymph Node Metastases Are Independent Factors of Poor Prognosis in Patients With Stages II to III Lung Adenocarcinoma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2023
    Article
  14. Retrospective Analysis of the Predictive Value ofDiagnostics (Basel, Switzerland) · 2023
    Article
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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

27 authors at 2 institutions in 1 country.

Neal AkhaveDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Jiexin ZhangDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Erin BayleyDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Meredith FrankDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Shin-Heng ChiouRutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, 195 Little Albany St, New Brunswick, NJ 08901, USA.
Carmen BehrensDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Runzhe ChenDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Xin HuDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Edwin Roger ParraDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Won-Chul LeeDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Stephen SwisherDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Luisa SolisDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Annikka WeissferdtDepartment of Epidemiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA; Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Cesar MoranDepartment of Epidemiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA; Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Neda KalhorDepartment of Epidemiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA; Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Jianhua ZhangDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Paul ScheetDepartment of Epidemiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA; Department of Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Ara A VaporciyanDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Boris SepesiDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Don L GibbonsDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
John V HeymachDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Jack J LeeDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Ignacio I WistubaDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
P Andrew FutrealDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA.
Jianjun ZhangDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA. Electronic address: jzhang20@mdanderson.org.
Junya FujimotoDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA. Electronic address: jfujimot@mdanderson.org.
Alexandre ReubenDepartment of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030, USA. Electronic address: areuben@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USRutgers, The State University of New Jersey · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
UNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HEYMACH, JOHN V., MINNA, JOHN D. · 1996 to 2024
$57.4M
NCI NIH HHS P30 CA016672NCI NIH HHS P50 CA070907
6 · The paper itself

Abstract

objectivesPathologists have routinely observed distinct histologic patterns of growth in early-stage lung adenocarcinoma (LUAD), which have been suggested to be associated with prognosis. Herein, we investigated the relationship between LUAD patterns of growth, as defined by the updated international association for the study of lung cancer (IASLC) grading criteria, and differences in the tumor immune microenvironment to identify predictors of response to immunotherapy.

methods174 resected stage I-III LUAD tumors were classified by histologic pattern of growth (i.e. solid, micropapillary, acinar, papillary, and lepidic) and then grouped as well differentiated, moderately differentiated, and poorly differentiated. Comprehensive multiplatform analysis including whole exome sequencing, gene expression profiling, immunohistochemistry, CIBERSORT, and T-cell receptor sequencing was performed and groups were compared for differences in genomic drivers, immune cell infiltrate, clonality, and survival. Finally, multivariate analysis was performed adjusting for pathologic stage and smoking status.

resultsPoorly differentiated tumors demonstrated a strong association with smoking relative to moderately differentiated or well differentiated tumors. However, unlike in prior reports, poorly differentiated tumors were not associated with a worse survival after curative-intent resection. Genomic analysis revealed that poorly differentiated tumors are associated with high tumor mutation burden but showed no association with oncogenic drivers. Immune analyses revealed that poorly differentiated tumors are associated with increased T-cell clonality, expression of PD-L1, and infiltration by cytotoxic CD8 T-cells, activated CD4 T-cells, and pro-inflammatory (M1) macrophages. Finally, multivariate analysis controlling for stage and smoking status confirmed independence of immune differences between IASLC grade groups.

conclusionsPoorly differentiated tumors, as defined by the updated IASLC grading criteria, are associated with a distinct immunogenic tumor microenvironment that predicts for therapeutic response to immune agents, including checkpoint inhibitors, and should be included in the clinical trial design of immunotherapy studies in early-stage lung adenocarcinoma.

Indexed as

AdenocarcinomaAdenocarcinoma of LungLung NeoplasmsB7-H1 AntigenBiomarkers, TumorHumansPrognosisTumor MicroenvironmentB7-H1 AntigenBiomarkers, TumorAdenocarcinoma patterns of growthImmune microenvironmentLung adenocarcinomaMultiplatform profilingPredictors of immunotherapy responseTranslational pathology

Identifiers

PMID35973335
PMCPMC10274087
OpenAlexW4291733874

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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.