Evidence map›Paper›PMID 35090171›Full record

ArticleBlood2022

Targeting cancer-associated fibroblasts in the bone marrow prevents resistance to CART-cell therapy in multiple myeloma.

Reona Sakemura, Mehrdad Hefazi, Elizabeth L Siegler, Michelle J Cox, Daniel P Larson, Michael J Hansen, Claudia Manriquez Roman, Kendall J Schick, Ismail Can, Erin E Tapper and 13 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed
13.0field-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

113 citing papers in PubMed, 133 citations in OpenAlex.

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  16. FAPαAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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53 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 2 institutions in 2 countries.

Reona SakemuraT Cell Engineering.ORCID 0000-0002-0293-5577
Mehrdad HefaziT Cell Engineering.
Elizabeth L SieglerT Cell Engineering.ORCID 0000-0002-8336-4373
Michelle J CoxT Cell Engineering.ORCID 0000-0002-2984-0834
Daniel P LarsonDivision of Hematopathology.ORCID 0000-0002-2938-922X
Michael J HansenDepartment of Immunology.
Claudia Manriquez RomanT Cell Engineering.ORCID 0000-0003-0082-9735
Kendall J SchickT Cell Engineering.
Ismail CanT Cell Engineering.ORCID 0000-0003-0569-5326
Erin E TapperT Cell Engineering.
Paulina HorveiT Cell Engineering.
Mohamad M AdadaT Cell Engineering.
Evandro D BezerraT Cell Engineering.ORCID 0000-0002-8978-5697
Lionel Aurelien Kankeu FonkouaT Cell Engineering.ORCID 0000-0001-5560-2103
Michael W RuffT Cell Engineering.
Wendy K NevalaDepartment of Immunology.
Denise K WaltersDepartment of Immunology.
Sameer A ParikhDivision of Hematology.ORCID 0000-0002-3221-7314
Yi LinDivision of Hematology.
Diane F JelinekDepartment of Immunology.
Neil E KayDivision of Hematology.ORCID 0000-0002-5951-5055
P Leif BergsagelDepartment of Hematology/Oncology, Mayo Clinic, Scottsdale, AZ.ORCID 0000-0003-1523-7388
Saad S KenderianT Cell Engineering.
Institute of Molecular Medicine · INMayo Clinic in Arizona · US

Funding

Project 4: Targeting Resistance to T-Cell Directed Therapy in Multiple MyelomaP50CA186781 · NCI · MAYO CLINIC ARIZONA · PI Peter Leif Bergsagel · 2015 to 2026
$25.5M
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 K99 CA273304NCI NIH HHS P50 CA186781
6 · The paper itself

Abstract

Pivotal clinical trials of B-cell maturation antigen-targeted chimeric antigen receptor T (CART)-cell therapy in patients with relapsed/refractory multiple myeloma (MM) resulted in remarkable initial responses, which led to a recent US Food and Drug Administration approval. Despite the success of this therapy, durable remissions continue to be low, and the predominant mechanism of resistance is loss of CART cells and inhibition by the tumor microenvironment (TME). MM is characterized by an immunosuppressive TME with an abundance of cancer-associated fibroblasts (CAFs). Using MM models, we studied the impact of CAFs on CART-cell efficacy and developed strategies to overcome CART-cell inhibition. We showed that CAFs inhibit CART-cell antitumor activity and promote MM progression. CAFs express molecules such as fibroblast activation protein and signaling lymphocyte activation molecule family-7, which are attractive immunotherapy targets. To overcome CAF-induced CART-cell inhibition, CART cells were generated targeting both MM cells and CAFs. This dual-targeting CART-cell strategy significantly improved the effector functions of CART cells. We show for the first time that dual targeting of both malignant plasma cells and the CAFs within the TME is a novel strategy to overcome resistance to CART-cell therapy in MM.

Indexed as

Cancer-Associated FibroblastsMultiple MyelomaBone MarrowCell- and Tissue-Based TherapyFibroblastsHumansImmunotherapy, AdoptiveTumor Microenvironment

Identifiers

PMID35090171
PMCPMC11290597
OpenAlexW4210632802

What OpenQuestion holds

Textmetadata
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.