Evidence map›Paper›PMID 42754891›Full record

ArticleMolecular cancer2026

Redifferentiation-enabled TSHRCART cells overcome antigen loss in aggressive thyroid cancers.

Claudia Manriquez-Roman, Elizabeth L Siegler, Justyna J Gleba, Truc N Huynh, Grace E DeFranco, Aylin Alasonyalilar Demirer, Matthew L Pawlush, Michael Redig, Skyeler M Klinge, Long K Mai and 22 more

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Article in Molecular cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

32 authors.

Claudia Manriquez-RomanCenter for Regenerative Biotherapeutics, Mayo Clinic, Rochester, MN, USA.
Elizabeth L SieglerCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
Justyna J GlebaCancer Biology Department, Mayo Clinic, Jacksonville, FL, USA.
Truc N HuynhCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
Grace E DeFrancoCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
Aylin Alasonyalilar DemirerCancer Biology Department, Mayo Clinic, Jacksonville, FL, USA.
Matthew L PawlushCancer Biology Department, Mayo Clinic, Jacksonville, FL, USA.
Michael RedigCancer Biology Department, Mayo Clinic, Jacksonville, FL, USA.
Skyeler M KlingeCancer Biology Department, Mayo Clinic, Jacksonville, FL, USA.
Long K MaiCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
James L MillerCancer Biology Department, Mayo Clinic, Jacksonville, FL, USA.
Erin E MillerCancer Biology Department, Mayo Clinic, Jacksonville, FL, USA.
Brooke L KimballCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
Erin E TapperCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
R Leo SakemuraCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
Carli M StewartCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
Ismail CanCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
Olivia L SirpillaCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
Jennifer M FeiginCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
Kun YunCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
Omar L Gutierrez-RuizCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
Hong XiaCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
Mehrdad HefaziCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
Kendall J SchickCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
Ekene J OgbodoCell Engineering Laboratory, Mayo Clinic, Rochester, MN, USA.
Gloria OlivierDepartment of Business Development, Mayo Clinic, Rochester, MN, USA.
Yushi QiuCancer Biology Department, Mayo Clinic, Jacksonville, FL, USA.
Robert C SmallridgeDivision of Endocrinology, Internal Medicine Department, Mayo Clinic, Jacksonville, FL, USA.
Abba ZubairDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL, USA.
Han W TunHematology/Oncology Division, Department of Medicine, Mayo Clinic, Jacksonville, FL, USA.
John A CoplandCancer Biology Department, Mayo Clinic, Jacksonville, FL, USA. copland.john@mayo.edu.
Saad S KenderianCenter for Regenerative Biotherapeutics, Mayo Clinic, Rochester, MN, USA. Kenderian.saad@mayo.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAntigen loss remains a major barrier to chimeric antigen receptor (CAR) T cell efficacy in solid tumors. In aggressive thyroid cancers, dedifferentiation is accompanied by coordinated loss of lineage-restricted surface antigens, limiting immune recognition.

methodsThyroid-stimulating hormone receptor (TSHR) expression was assessed on multiple histotypes of thyroid cancer via immunohistochemistry. TSHR-directed chimeric antigen receptor T (CART) cell therapy was assessed against differentiated thyroid cancer subtypes which highly expressed TSHR and dedifferentiated thyroid cancer subtypes which downregulated TSHR in vitro and in xenograft and patient-derived xenograft (PDX) mouse models. MAPK inhibitors were assessed in combination with TSHR-CART cell therapy in dedifferentiated thyroid cancers which downregulated TSHR in vitro and in PDX mouse models.

resultsUsing TSHR as a clinically relevant antigen target, we demonstrated that pharmacologic tumor redifferentiation can restore target expression and sensitize tumors to CART cell therapy. TSHR-CART cells mediate durable antigen-specific cytotoxicity in TSHRhigh differentiated thyroid cancer models but are limited in TSHRlow dedifferentiated tumors. In patient-derived anaplastic thyroid cancer xenografts, MAPK inhibition restores TSHR expression and converts tumors from CAR-resistant to CAR-responsive. Concurrent redifferentiation therapy and CART cell treatment yields superior tumor control and survival versus monotherapy, without impairing CART cell function.

conclusionsThese findings establish tumor redifferentiation as a generalizable strategy to overcome antigen loss and enhance CART cell therapy in thyroid cancer and potentially other solid tumors.

Indexed as

Immunotherapy, AdoptiveReceptors, Chimeric AntigenReceptors, ThyrotropinThyroid NeoplasmsAnimalsCell DifferentiationCell Line, TumorDisease Models, AnimalHumansMiceXenograft Model Antitumor AssaysReceptors, Chimeric AntigenReceptors, ThyrotropinCancer immunotherapyCART cell therapyRedifferentiation therapyThyroid cancer

Identifiers

PMID42754891
PMCPMC13584383

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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.