Evidence map›Paper›PMID 37730274›Full record

ArticleJournal for immunotherapy of cancer2023

CCL21-DC in situ vaccination in murine NSCLC overcomes resistance to immunotherapy and generates systemic tumor-specific immunity.

Ramin Salehi-Rad, Raymond J Lim, Yushen Du, Linh M Tran, Rui Li, Stephanie L Ong, Zi Ling Huang, Camelia Dumitras, Tianhao Zhang, Stacy J Park and 12 more

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

Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

25 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Natural and Engineered Cytokines as Cancer Therapeutics.Annual review of cancer biology · 2026
    Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. 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
    Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Review
  19. Review
  20. 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

22 authors at 1 institution in 2 countries.

Ramin Salehi-Rad *Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.ORCID 0000-0003-1543-5421
Raymond J Lim *Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Yushen DuMolecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Linh M TranMedicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Rui LiMedicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.ORCID 0000-0002-5620-4833
Stephanie L OngMedicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Zi Ling HuangMedicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Camelia DumitrasMedicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Tianhao ZhangMolecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Stacy J ParkMedicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
William CrossonMolecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Bitta KahangiMedicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Jensen AbascalMedicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Christopher SeetMedicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Michael OhMedicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Maryam ShabihkhaniPathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Manash PaulMedicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.ORCID 0000-0002-9404-0024
Kostyantyn KrysanMedicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Aaron E LisbergMedicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Edward B GaronMedicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.ORCID 0000-0001-7077-8801
Bin LiuMedicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA sdubinett@mednet.ucla.edu bliu@mednet.ucla.edu.
Steven M DubinettMedicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA sdubinett@mednet.ucla.edu bliu@mednet.ucla.edu.
University of California, Los Angeles · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Damoiseaux · 1985 to 2026
$134.5M
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ZACK, JEROME A. · 1991 to 2018
$39.9M
UCLA Pulmonary and Critical Care Medicine Training ProgramT32HL072752 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JOHN A BELPERIO, TOMAS GANZ · 2003 to 2026
$8.3M
Integrated Molecular, Cellular, and Imaging Characterization of Screen-Detected Lung CancerU01CA196408 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ABERLE, DENISE R., DUBINETT, STEVEN M. · 2015 to 2021
$7.1M
Intratumoral Administration of CCL21-gene Modified Dendritic Cell With Intravenous Pembrolizumab for Advanced NSCLCK08CA245249 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LISBERG, AARON ELLIOTT · 2020 to 2024
$1.3M
Evaluation of a therapeutic vaccination strategy with motif neoepitope peptide-pulsed autologous dendritic cells for non-small cell lung cancer patients harboring a charged HLA-B binding pocket.R21CA277172 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GARON, EDWARD B, LIU, BIN · 2023 to 2024
$393k
BLRD VA IK2 BX006194NCATS NIH HHS UL1 TR001881NCI NIH HHS K08 CA245249NCI NIH HHS P30 CA016042NCI NIH HHS R21 CA277172NCI NIH HHS U01 CA196408NHLBI NIH HHS T32 HL072752NIAID NIH HHS P30 AI028697
6 · The paper itself

Abstract

backgroundDespite recent advances in immunotherapy, many patients with non-small cell lung cancer (NSCLC) do not respond to immune checkpoint inhibitors (ICI). Resistance to ICI may be driven by suboptimal priming of antitumor T lymphocytes due to poor antigen presentation as well as their exclusion and impairment by the immunosuppressive tumor microenvironment (TME). In a recent phase I trial in patients with NSCLC, in situ vaccination (ISV) with dendritic cells engineered to secrete CCL21 (CCL21-DC), a chemokine that facilitates the recruitment of T cells and DC, promoted T lymphocyte tumor infiltration and PD-L1 upregulation.

methodsMurine models of NSCLC with distinct driver mutations (

resultsISV with CCL21-DC sensitized immune-resistant murine NSCLCs to ICI and led to the establishment of tumor-specific immune memory. Immunophenotyping revealed that CCL21-DC obliterated tumor-promoting neutrophils, promoted sustained infiltration of CD8 cytolytic and CD4 Th1 lymphocytes and enriched progenitor T cells in the TME. Addition of ICI to CCL21-DC further enhanced the expansion and effector function of T cells both locally and systemically. Longitudinal evaluation of tumor mutation profiles revealed that CCL21-DC plus ICI induced immunoediting of tumor subclones, consistent with the broadening of tumor-specific T cell responses.

conclusionsCCL21-DC ISV synergizes with anti-PD-1 to eradicate murine NSCLC. Our data support the clinical application of CCL21-DC ISV in combination with checkpoint inhibition for patients with NSCLC.

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsAnimalsChemokine CCL21HumansImmunotherapyMiceProto-Oncogene Proteins p21(ras)Tumor MicroenvironmentTumor Suppressor Protein p53CCL21 protein, humanChemokine CCL21Proto-Oncogene Proteins p21(ras)Tumor Suppressor Protein p53Dendritic CellsImmunotherapyNon-Small Cell Lung CancerTumor MicroenvironmentVaccination

Identifiers

PMID37730274
PMCPMC10510892
OpenAlexW4386897732

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.