Evidence map›Paper›PMID 30771521›Full record

ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2019

The Combination of MEK Inhibitor With Immunomodulatory Antibodies Targeting Programmed Death 1 and Programmed Death Ligand 1 Results in Prolonged Survival in Kras/p53-Driven Lung Cancer.

Jong Woo Lee, Yu Zhang, Kyung Jin Eoh, Roshan Sharma, Miguel F Sanmamed, Jenny Wu, Justin Choi, Hee Sun Park, Akiko Iwasaki, Edward Kaftan and 4 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 5% 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

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
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  5. Article
  6. Article
  7. Article
  8. Article
  9. Precision immune regulation in KRAS-mutated cancers: the final piece of the puzzle?Journal of experimental & clinical cancer research : CR · 2025
    Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Emerging Targets in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2024
    Review
  18. Article
  19. Review
  20. RAF and MEK Inhibitors in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2024
    Review
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

14 authors at 5 institutions in 2 countries.

Jong Woo LeeSection of Medical Oncology, Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut.
Yu ZhangDepartment of Immunobiology, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut.
Kyung Jin EohSection of Medical Oncology, Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut; Department of Obstetrics and Gynecology, Yonsei University College of Medicine, Seoul, South Korea.
Roshan SharmaSection of Medical Oncology, Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut.
Miguel F SanmamedDepartment of Immunobiology, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut.
Jenny WuSection of Medical Oncology, Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut.
Justin ChoiSection of Medical Oncology, Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut.
Hee Sun ParkDepartment of Internal Medicine, Chungnam National University Hospital, Daejeon, South Korea.
Akiko IwasakiDepartment of Immunobiology and Molecular, Cellular and Developmental Biology, Yale School of Medicine, New Haven, Connecticut.
Edward KaftanSection of Medical Oncology, Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut.
Lieping ChenDepartment of Immunobiology, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut.
Vali PapadimitrakopoulouDepartment of Thoracic, Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
Roy S HerbstSection of Medical Oncology, Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut.
Ja Seok KooSection of Medical Oncology, Department of Internal Medicine, Yale Comprehensive Cancer Center, Yale School of Medicine, New Haven, Connecticut; Developmental Therapeutics Translational Research Program, Yale Comprehensive Cancer Center, New Haven, Connecticut. Electronic address: jpeter.koo@yale.edu.
Yale Cancer Center · USChungnam National University Hospital · KRThe University of Texas MD Anderson Cancer Center · USYale University · USYonsei University · KR

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI DAVID L RIMM · 1985 to 2026
$85.0M
Yale SPORE in Lung Cancer (YSILC): The Biology and Personalized Treatment of Lung CancerP50CA196530 · NCI · YALE UNIVERSITY · PI Shuangge Ma · 2015 to 2026
$31.1M
Role of CREB in Lung Cancer DevelopmentR01CA126801 · NCI · YALE UNIVERSITY · PI KOO, JA SEOK · 2010 to 2014
$1.6M
NCATS NIH HHS UL1 TR001863NCI NIH HHS P30 CA016359NCI NIH HHS P50 CA196530NCI NIH HHS R01 CA126801
6 · The paper itself

Abstract

introductionThis study aimed to characterize the tumor-infiltrating immune cells population in Kras/tumor protein 53 (Trp53)-driven lung tumors and to evaluate the combinatorial antitumor effect with MEK inhibitor (MEKi), trametinib, and immunomodulatory monoclonal antibodies (mAbs) targeting either programmed death -1 (PD-1) or programmed cell death ligand 1 (PD-L1) in vivo.

methodsTrp53

resultsMyeloid-derived suppressor cells (MDSCs) were significantly augmented in PKL-driven lung tumors compared to normal lungs of tumor-free mice. PD-L1 expression appeared to be highly positive in both lung tumor cells and, particularly MDSCs. The combinatory administration of MEKi with either anti-PD-1 or anti-PD-L1 mAbs synergistically increased antitumor response and survival outcome compared with single-agent therapy in both the PKL-mediated syngeneic and transgenic lung cancer models. Theses combinational treatments resulted in significant increases of tumor-infiltrating CD8

conclusionsThese findings suggest a potential therapeutic approach for untargetable Kras/p53-driven lung cancers with synergy between targeted therapy using MEKi and immunotherapies.

Indexed as

Adenocarcinoma of LungAnimalsAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenDrug SynergismFemaleLung NeoplasmsMAP Kinase Kinase KinasesMiceMice, KnockoutMice, TransgenicMyeloid-Derived Suppressor CellsProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsProto-Oncogene Proteins p21(ras)Antineoplastic Agents, ImmunologicalB7-H1 AntigenCd274 protein, mouseHras protein, mouseMAP Kinase Kinase KinasesPdcd1 protein, mouseProgrammed Cell Death 1 ReceptorProtein Kinase InhibitorsProto-Oncogene Proteins p21(ras)PyridonesPyrimidinonestrametinibTrp53 protein, mouseTumor Suppressor Protein p53Kras/p53-driven lung cancerMyeloid-derived suppressor cellsProgrammed death 1Programmed death ligand 1Trametinib

Identifiers

PMID30771521
PMCPMC6542636
OpenAlexW2914170573

What OpenQuestion holds

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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.