Evidence map›Paper›PMID 37378662›Full record

ArticleCancer immunology research2023

AXL Inhibition Improves the Antitumor Activity of Chimeric Antigen Receptor T Cells.

R Leo Sakemura, Mehrdad Hefazi, Michelle J Cox, Elizabeth L Siegler, Sutapa Sinha, Michael J Hansen, Carli M Stewart, Jennifer M Feigin, Claudia Manriquez Roman, Kendall J Schick and 21 more

Open access · greenAbstract read
In one paragraph

Article in Cancer immunology research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

13 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
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  8. Article
  9. Article
  10. AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025
    Review
  11. Review
  12. Review
  13. Article
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

31 authors at 2 institutions in 1 country.

R Leo SakemuraT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0002-0293-5577
Mehrdad HefaziT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0001-8860-3380
Michelle J CoxT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0002-2984-0834
Elizabeth L SieglerT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0002-8336-4373
Sutapa SinhaDivision of Hematology, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0002-7274-9622
Michael J HansenDepartment of Immunology, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0001-7712-0375
Carli M StewartT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0002-2288-2230
Jennifer M FeiginT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0009-0000-6499-4655
Claudia Manriquez RomanT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0003-0082-9735
Kendall J SchickT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0001-5744-3863
Ismail CanT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0003-0569-5326
Erin E TapperT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0002-0383-0806
Paulina HorveiT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0009-0006-6774-1542
Mohamad M AdadaT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0002-2988-2081
Evandro D BezerraT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0002-8978-5697
Lionel Aurelien Kankeu FonkouaT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0001-5560-2103
Michael W RuffT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0001-8513-9615
Cynthia L ForsmanT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0009-0009-6100-9213
Wendy K NevalaDepartment of Immunology, Mayo Clinic, Rochester, Minnesota.ORCID 0009-0004-2256-6715
Justin C BoysenDivision of Hematology, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0002-4398-1174
Renee C TschumperDepartment of Immunology, Mayo Clinic, Rochester, Minnesota.ORCID 0009-0009-6595-1919
Cory L GrandSumitomo Dainippon Pharma Oncology, Inc. Lehi, Utah.ORCID 0009-0007-4458-3745
Kameswara R KuchimanchiSumitomo Dainippon Pharma Oncology, Inc. Lehi, Utah.ORCID 0009-0003-3288-3450
Lars MouritsenSumitomo Dainippon Pharma Oncology, Inc. Lehi, Utah.ORCID 0009-0001-7401-0303
Jason M FoulksSumitomo Dainippon Pharma Oncology, Inc. Lehi, Utah.ORCID 0000-0002-7883-2347
Steven L WarnerSumitomo Dainippon Pharma Oncology, Inc. Lehi, Utah.ORCID 0000-0002-6596-1676
Timothy G CallDivision of Hematology, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0002-8465-9587
Sameer A ParikhDivision of Hematology, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0002-3221-7314
Wei DingDivision of Hematology, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0001-9811-4601
Neil E KayDivision of Hematology, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0002-5951-5055
Saad S KenderianT Cell Engineering, Mayo Clinic, Rochester, Minnesota.ORCID 0000-0003-2767-3830
Mayo Clinic · USSumitomo Dainippon Pharma (United States) · US

Funding

Paul Calabresi Program in Clinical/Translational Research at Mayo ClinicK12CA090628 · NCI · MAYO CLINIC ROCHESTER · PI WEROHA, SARAVUT · 2001 to 2025
$19.7M
Towards Safer and More Effective CART Cell Therapy Through the Modulation of Myeloid CytokinesR37CA266344 · NCI · MAYO CLINIC ROCHESTER · PI Saad J. Kenderian · 2022 to 2026
$3.5M
Targeting Cancer-Associated Fibroblasts Prevents Resistance to Chimeric Antigen Receptor T Cell TherapyK99CA273304 · NCI · MAYO CLINIC ROCHESTER · PI SAKEMURA, REONA · 2022 to 2023
$342k
NCI NIH HHS K12 CA090628NCI NIH HHS K99 CA273304NCI NIH HHS R37 CA266344
6 · The paper itself

Abstract

The receptor tyrosine kinase AXL is a member of the TYRO3, AXL, and proto-oncogene tyrosine-protein kinase MER family and plays pleiotropic roles in cancer progression. AXL is expressed in immunosuppressive cells, which contributes to decreased efficacy of immunotherapy. Therefore, we hypothesized that AXL inhibition could serve as a strategy to overcome resistance to chimeric antigen receptor T (CAR T)-cell therapy. To test this, we determined the impact of AXL inhibition on CD19-targeted CAR T (CART19)-cell functions. Our results demonstrate that T cells and CAR T cells express high levels of AXL. Specifically, higher levels of AXL on activated Th2 CAR T cells and M2-polarized macrophages were observed. AXL inhibition with small molecules or via genetic disruption in T cells demonstrated selective inhibition of Th2 CAR T cells, reduction of Th2 cytokines, reversal of CAR T-cell inhibition, and promotion of CAR T-cell effector functions. AXL inhibition is a novel strategy to enhance CAR T-cell functions through two independent, but complementary, mechanisms: targeting Th2 cells and reversing myeloid-induced CAR T-cell inhibition through selective targeting of M2-polarized macrophages.

Indexed as

NeoplasmsReceptors, Chimeric AntigenAxl Receptor Tyrosine KinaseHumansProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesAxl Receptor Tyrosine KinaseProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesReceptors, Chimeric Antigen

Identifiers

PMID37378662
PMCPMC10530462
OpenAlexW4382345239

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.