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Cited by 1CAR-T cell therapy researchImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

Ectopic PU.1 Expression Provides Chimeric Antigen Receptor (CAR) T Cells with Innate Cell Capacities Including IFN-β Release

Open access
Harrer, Dennis Christoph, Eder, Matthias, Barden, Markus, Pan, Hong, Herr, Wolfgang, Abken, Hinrich·2024·Cancers
DOI 10.3390/cancers16152737PMC PMC11311516
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Abstract

Chimeric antigen receptor (CAR) T cell therapy has achieved extraordinary success in eliminating B cell malignancies; however, so far, it has shown limited efficacy in the treatment of solid tumors, which is thought to be due to insufficient CAR T cell activation. We hypothesized that the transcription factor PU.1, a master regulator of innate cell functionality, may augment pro-inflammatory CAR T cell activation. T cells were engineered with a CEA-specific CAR together with the constitutive expression of PU.1. CAR-redirected T cell activation was recorded for canonical functionality in vitro under conditions of prolonged repetitive antigen exposure. Ectopic PU.1 expression in CAR T cells upregulated the costimulatory receptors CD40, CD80, CD86, and CD70, which, unexpectedly, did not augment effector functions but hampered the upregulation of 4-1BB, decreased IL-2 production, reduced CAR T cell proliferation, and impaired their cytotoxic capacities. Under “stress” conditions of repetitive engagement of cognate tumor cells, CAR T cells with ectopic PU.1 showed reduced persistence, and finally failed to control the growth of cancer cells. Mechanistically, PU.1 caused CAR T cells to secrete IFN-β, a cytokine known to promote CAR T cell attrition and apoptosis. Collectively, PU.1 can polarize the functional capacities of CAR T cells towards innate cells.

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Written from the paper’s full text.

TL;DR

Ectopic PU.1 expression in CEA-specific CAR T cells upregulated multiple costimulatory receptors but unexpectedly impaired IL-2 secretion, proliferation, cytotoxicity, and persistence under repetitive antigen exposure, with CAR-triggered IFN-β release as a likely mechanism. These findings suggest PU.1 polarizes CAR T cells toward innate-like capacities that are detrimental to canonical CAR T cell function.

Key findings

  • PU.1-expressing aCEA-28ζ-PU.1 CAR T cells upregulated MHC-I/II, costimulatory receptors CD40, CD70, CD80, and CD86, adhesion molecule CD54, and myeloid marker CD33 after CAR stimulation in both CD4+ and CD8+ T cells; CAR surface levels were similar to control and cells were enriched to >90% CAR+.
  • Despite costimulatory receptor upregulation, PU.1 did not increase CD25 upregulation or IFN-γ release, but significantly decreased IL-2 secretion upon co-culture with CEA+ BxPC-3 cells and reduced proliferation of CD8+ and CD4+ CAR T cells over a five-day stimulation period.
  • PU.1 reduced CAR-triggered CD137 upregulation and cytotoxicity against BxPC-3 cells across effector-to-target ratios, without major differences in granzyme B or perforin levels; in repetitive stimulation, control CAR T cells eliminated BxPC-3 in both rounds, whereas PU.1 CAR T cells contracted, showed increased annexin V staining, lower Ki-67, and failed to control tumor growth.
  • PU.1 CAR T cells released substantial IFN-β after CAR stimulation, whereas control CAR T cells did not spontaneously produce IFN-β; the authors propose this as a key factor limiting functional persistence.

Methods

  • Human T cells from healthy donor PBMCs were activated with OKT-3, anti-CD28 mAb, and IL-2, then retrovirally transduced with a CEA-specific CAR (BW431/26scFv-Fc-CD28-ζ) linked via P2A to either PU.1 or GFP; CAR T cells were MACS-enriched to >90% CAR+ and rested in IL-2-free medium for assays.
  • In vitro co-cultures used CEA+ BxPC-3 pancreatic cancer cells and CEA− 293T cells; readouts included Western blot, flow cytometry (surface/intracellular staining, annexin V, Ki-67, proliferation dye), ELISA for IL-2, IFN-γ, and IFN-β, XTT cytotoxicity assays, and a repetitive stimulation assay.
  • Statistical analysis used GraphPad Prism 9 with Student’s t test or paired t test as specified; significance thresholds were *p ≤ 0.05, p ≤ 0.01, *p ≤ 0.001, and p ≤ 0.0001.

Limitations

  • Stated limitations: Not stated in the paper.
  • Evident from the text: all functional data are in vitro, using one CEA-specific CAR, CEA+ BxPC-3 and CEA− 293T target cells, and healthy donor PBMCs; no in vivo tumor model or patient samples are reported.
  • Evident from the text: the mechanistic link between PU.1-driven IFN-β release and impaired CAR T cell persistence is proposed and correlative; IFN-β blockade or knockout rescue experiments are not shown.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.3390/cancers16152737

Cites

28 of 28 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

14 of 21 cited sources checked · 6 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    Poor CAR T cell activity against solid tumors has been attributed to insufficient activation and proliferation of modified T cells, as well as to their limited persistence.

    “Poor CAR T cell activity against solid tumors has been attributed to the insufficient activation and proliferation of modified T cells, as well as to their limited persistence [2].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [2] Marofi, 2022, Hurdles to breakthrough in CAR T cell therapy of solid tumors, Stem Cell Res. Ther. source
  • Premisecitation

    CAR T cell products with durable anti-cancer activity are not yet available for solid tumors.

    “However, in the large realm of solid tumors, CAR T cell products with durable anti-cancer activity are not yet available [1].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [1] Holzinger, 2022, Treatment with Living Drugs: Pharmaceutical Aspects of CAR T Cells, Pharmacology source
  • Premisecitation

    PU.1 confers an inflammatory phenotype to B cells and macrophages.

    “By initiating the expression of pro-inflammatory cytokines, PU.1 confers an inflammatory phenotype to B cells and macrophages [12,13,14].”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [12] Feng, 2008, 1 and C/EBPalpha/beta convert fibroblasts into macrophage-like cells, Proc. Natl. Acad. Sci. USA source
    • cites [13] Casero, 2018, Differential Expression of PU.1 and Key T Lineage Transcription Factors Distinguishes Fetal and Adult T Cell Development, J. Immunol. source

      The Introduction describes PU.1’s role in T-cell regulatory genes, and the Discussion discusses its regulation of CD127 expression. Neither addresses pro-inflammatory cytokine production or an inflammatory phenotype in B cells or macrophages. Searches for those cell types, cytokines, and inflammation found no supporting passage in our copy. (LLM, conf=0.77)

      Experimental — accuracy not yet measured
    • cites [14] Yashiro, 2019, A transcription factor PU.1 is critical for Ccl22 gene expression in dendritic cells and macrophages, Sci. Rep. source

      The Discussion (page not provided) shows that PU.1 regulates Ccl22 expression in macrophages, but identifies Ccl22 as an M2 macrophage marker rather than evidence that PU.1 confers an inflammatory phenotype. The Introduction (page not provided) mentions PU.1 in B-cell development and TNF-α regulation in dendritic cells; it does not establish pro-inflammatory cytokine expression or an inflammatory phenotype in B cells and macrophages. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation

    PU.1 upregulates costimulatory receptors such as CD80 and CD86.

    “For upregulating costimulatory receptors, such as CD80 and CD86, PU.1 (Purine Rich Box-1) is a crucial key factor that also controls antigen presentation and the induction of type-I interferon [10].”
    • Also stated in: § 4. Discussion · boosted
      “PU.1 is a major trigger in upregulating multiple costimulatory receptors, such as CD80 and CD86, both on γδ T cells and on conventional αβ T cells [24].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [10] Chopin, 2019, Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT, Immunity source
    • cites [24] Muto, 2015, Myeloid molecular characteristics of human γδ T cells support their acquisition of tumor antigen-presenting capacity, Cancer Immunol. Immunother. source

      The transcription-factor comparison (p. 6) measures PU.1 expression but does not test whether PU.1 upregulates CD80 or CD86. The signaling-pathway results (p. 5) examine MAPK and NFκB instead; the searched passages also do not link PU.1 to type-I interferon induction. (LLM, conf=0.74)

      Experimental — accuracy not yet measured
  • Findingown data

    Ki-67 staining revealed that PU.1 CAR T cells suffered from an inferior proliferative capacity compared to control CAR T cells.

    “Staining for Ki-67 in response to stimulation with BxPC-3 cells revealed that aCEA-28ζ-PU.1 CAR T cells suffered from an inferior proliferative capacity compared to control aCEA-28ζ-GFP CAR T cells (Figure 4C).”
    Quote in the paperSubstantial claim
  • May combine two claims. 13
  • Classified as probably not a substantial claim. 9

  • May combine two claims.

    Premisecitation

    Type-I IFN augmented apoptosis and confined the anti-tumor activity of CAR T cells during repetitive rounds of antigen stimulation.

    “Previously, we demonstrated that type-I IFN augmented apoptosis and confined the anti-tumor activity of CAR T cells during repetitive rounds of antigen stimulation [17], which is similar to CAR T cells with ectopic PU.1 expression.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [17] Harrer, D.C., Schenkel, C., Bezler, V., Kaljanac, M., Hartley, J., Barden, M., Pan, H., Holzinger, A., Herr, W., and Abken, H. (2022). CAR Triggered Release of Type-1 Interferon Limits CAR T-Cell Activities by an Artificial Negative Autocrine Loop. Cells, 11. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Efforts to improve functional CAR T cell performance have spawned CAR T cell products co-expressing additional costimulatory receptors.

    “Efforts to improve functional CAR T cell performance has spawned CAR T cell products co-expressing additional costimulatory receptors [3,4,5,6], including CD80/CD86-CD28 [3,5], 41BBL-CD137 [6], CD70-CD27 [7], and CD40-CD40L [8], or the constitutive active CD40/TLR4 [9].”
    Quote in the paperNot a substantial claim4 of 4 sources checked
    • cites [3] Dobrin, 2024, Synthetic dual co-stimulation increases the potency of HIT and TCR-targeted cell therapies, Nat. Cancer source
    • cites [4] Katsarou, 2021, Combining a CAR and a chimeric costimulatory receptor enhances T cell sensitivity to low antigen density and promotes persistence, Sci. Transl. Med. source
    • cites [5] Eyquem, 2022, HLA-independent T cell receptors for targeting tumors with low antigen density, Nat. Med. source

      The Results section (page not specified) says that co-expressing ligands for CD28 and 4-1BB had previously enhanced the persistence of CAR T cells. This supports the broader point about adding costimulatory support, but the co-expressed molecules described are ligands, not additional costimulatory receptors; this paper's own co-expression experiments used HIT T cells rather than CAR T cells. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [6] Zhao, 2015, Structural Design of Engineered Costimulation Determines Tumor Rejection Kinetics and Persistence of CAR T Cells, Cancer Cell source

      The Results describe CAR T-cell configurations that co-express costimulatory ligands, including 4-1BBL or CD80, to improve function. The Discussion distinguishes those ligands from the receptors they engage; this paper does not describe co-expression of additional costimulatory receptors. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    IFN-α and IFN-β have similar functionality, but IFN-β shows the highest receptor affinity, resulting in stronger IFN-driven effects.

    “While IFN-α and IFN-β have similar functionality, IFN-β shows the highest receptor affinity, resulting in stronger IFN-driven effects [27].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [27] Piehler, 2012, Structural and dynamic determinants of type I interferon receptor assembly and their functional interpretation, Immunol. Rev. source

      The Energetics and dynamics section identifies IFNβ as the tightest-binding IFN. The Systematic correlation section says its higher affinity explains greater antiproliferative activity than IFNα2, but also says their antiviral activity is very similar. The claim overgeneralizes this into stronger IFN-driven effects overall; page numbers were not supplied for these passages. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    IFN-β was reported to cause pronounced attrition of CAR T cells, leading to inferior survival of tumor-bearing mice treated with CAR T cells and IFN-β.

    “Moreover, IFN-β was reported to cause pronounced attrition of CAR T cells, leading to inferior survival of tumor-bearing mice treated with CAR T cells and IFN-β [28].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [28] Evgin, 2020, Oncolytic virus-derived type I interferon restricts CAR T cell therapy, Nat. Commun. source

      The Results sections ‘Type I IFN is deleterious to CAR T cells’ and ‘IFNβ elicits T cell intrinsic and CAR T specific effects’ link virus-associated IFNβ to CAR T-cell attrition and show that recombinant IFNβ increases CAR T-cell apoptosis. But ‘Combination therapy does not provide superior tumor control’ reports no improvement in survival with VSVmIFNβ plus CAR T cells, not inferior survival relative to CAR T cells alone. The mouse treatment also used an IFNβ-expressing virus, rather than IFNβ administered alone. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    PU.1 plays an important role in early T cell development, while in healthy adults, PU.1-directed actions are largely restricted to the myeloid and B cell compartment.

    “PU.1 plays an important role in early T cell development, while in healthy adults, PU.1-directed actions are largely restricted to the myeloid and B cell compartment [11].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [11] Rothenberg, E.V., Hosokawa, H., and Ungerbäck, J. (2019). Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development. Front. Immunol., 10. source

      The Introduction (§ PU.1 Expression in Precursors of T Cells; page unavailable) supports PU.1’s role in early T-cell development and says most mature T cells lack detectable PU.1. It also identifies PU.1 activity in dendritic cells and in early T-cell precursors in the postnatal thymus, so the proposed restriction of its actions in healthy adults to myeloid and B-cell compartments is not established by this source. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Premisecitation

    Optimizing appropriate costimulation remains a challenging task to propel modern CAR T cell therapy to the next level.

    “Optimizing appropriate costimulation remains a challenging task to propel modern CAR T cell therapy to the next level [19].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [19] Feucht, 2019, Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency, Nat. Med. source

  • May combine two claims.

    Findingown data

    PU.1 CAR T cells released substantial amounts of IFN-β following CAR stimulation through BxPC-3 cell engagement compared to control CAR T cells, whereas control CAR T cells did not spontaneously produce IFN-β.

    “Whereas CAR T cells physiologically did not spontaneously produce IFN-β, aCEA-28ζ-PU.1 CAR T cells released substantial amounts of IFN-β following CAR stimulation through BxPC-3 cell engagement as compared to control CAR T cells without PU.1 (Figure 4D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Control CAR T cells eliminated all BxPC-3 cells in both rounds of stimulation, whereas the cytotoxic capacity of PU.1 CAR T cells was markedly compromised.

    “Control aCEA-28ζ-GFP CAR T cells were able to eliminate all BxPC-3 cells in both rounds of stimulation, whereas the cytotoxic capacity of aCEA-28ζ-PU.1 CAR T cells was markedly compromised (Figure 4A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In repetitive stimulation, control CAR T cells expanded, while PU.1 CAR T cells did not proliferate but entered a contraction phase resulting in fewer surviving CAR T cells.

    “While control aCEA-28ζ-GFP CAR T cells expanded in a CAR-triggered fashion in response to sequential antigen stimulation, aCEA-28ζ-PU.1 CAR T cells did not proliferate but entered a contraction phase resulting in fewer surviving CAR T cells upon CAR stimulation as compared to control CAR T cells (Figure 4A).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Ectopic PU.1 expression induced pronounced upregulation of the adhesion molecule CD54 and the myeloid marker CD33.

    “Finally, the ectopic expression of PU.1 induced a pronounced upregulation of the adhesion molecule CD54 and the myeloid marker CD33 as compared to control CAR T cells, while the expression of the corresponding ligand CD11a did not significantly change (Figure 1D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    CAR T cells engineered with the aCEA-28ζ-P2A-PU.1 vector showed tangible PU.1 levels, and no PU.1 was detected in control aCEA-28ζ-GFP CAR T cells.

    “CAR T cells engineered with the aCEA-28ζ-P2A-PU.1 vector showed tangible PU.1 levels; no PU.1 was detected in control aCEA-28ζ-GFP CAR T cells.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Fluorescent-minus-one controls were used for gating.

    “Fluorescent-minus-one (FMO) controls were used for gating.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    PU.1 controls antigen presentation and the induction of type-I interferon.

    “PU.1 (Purine Rich Box-1) is a crucial key factor that also controls antigen presentation and the induction of type-I interferon [10].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Chopin, 2019, Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT, Immunity source

  • May combine two claims.

    Interpretationown data

    CAR T cells with ectopic PU.1 expression exhibited reduced functional persistence predicated on CAR T cell attrition, decreased cytotoxicity, enhanced apoptosis, and insufficient proliferative capacity, although costimulatory receptors were increased.

    “We concluded that CAR T cells with ectopic PU.1 expression exhibited a reduced functional persistence predicated on CAR T cell attrition in response to sequential antigen stimulation, decreased cytotoxicity, enhanced apoptosis, and an insufficient proliferative capacity, although costimulatory receptors like CD40, CD70, CD80, and CD86 were increased.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The in vitro repetitive antigen stimulation stress-test reflects the functional persistence of CAR T cells.
    • Rests on an assumption: The CEA+ BxPC-3 pancreatic cancer cell model is representative of solid tumors for CAR T cell therapy.

  • May combine two claims.

    Interpretationown data

    Ectopic PU.1 expression diminishes CAR-triggered cytotoxicity while preventing the upregulation of CD137.

    “In sum, the ectopic expression of PU.1 diminishes CAR-triggered cytotoxicity while preventing the upregulation of costimulatory molecules, such as CD137, which is required to unfold optimal CAR T cell cytotoxicity.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    PU.1 facilitates the expression of genes governing the interface of innate and adaptive immunity, such as IFN-β, along with a variety of costimulatory receptors.

    “Generally, PU.1 facilitates the expression of genes governing the interface of innate and adaptive immunity, such as IFN-β, along with a variety of costimulatory receptors [10,15].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [10] Chopin, 2019, Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT, Immunity source
    • cites [15] Turkistany, 2011, The transcription factor PU.1 is a critical regulator of cellular communication in the immune system, Arch. Immunol. Ther. Exp. source

  • May combine two claims.

    Interpretationown data

    Ectopic PU.1 expression upregulates multiple costimulatory receptors on CAR T cells; however, it induces IFN-β, compromising effector cell functionality.

    “The ectopic expression of the myeloid master regulator PU.1 upregulates multiple costimulatory receptors on CAR T cells; however, it induces IFN-β, compromising effector cell functionality.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Statistical analysis was performed using GraphPad Prism, and P values were determined by Student's t test or the paired t test as specified in the figure legend.

    “Statistical analysis was performed utilizing GraphPad Prism, Version 9 (GraphPad Software, San Diego, CA, USA). P values were determined by Student’s t test or the paired t test as specified in the figure legend; ns indicates not significant, * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, and **** p ≤ 0.0001.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    PU.1 is a master regulator of innate cell functionality.

    “We hypothesized that the transcription factor PU.1, a master regulator of innate cell functionality, may augment pro-inflammatory CAR T cell activation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Chopin, 2019, Transcription Factor PU.1 Promotes Conventional Dendritic Cell Identity and Function via Induction of Transcriptional Regulator DC-SCRIPT, Immunity source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    CAR T cells were enriched by magnetic cell sorting to a purity greater than 90% CAR+ cells for further analyses.

    “CAR T cells were further enriched by magnetic cell sorting (MACS) to a purity > 90% CAR+ cells for further analyses (Figure 1B).”
    Quote in the paperNot a substantial claim
20 of 20

  • The authors state this as an assumption.

    IFN-β release by aCEA-28ζ-PU.1 CAR T cells is a key factor limiting the functional persistence of CAR T cells with ectopic PU.1 expression.

    “We assume that IFN-β release by aCEA-28ζ-PU.1 CAR T cells is a key factor limiting the functional persistence of CAR T cells with ectopic PU.1 expression.”

  • The paper relies on this without support.

    The in vitro repetitive antigen stimulation stress-test reflects the functional persistence of CAR T cells.

    “We addressed the functional persistence of CAR T cells with and without ectopic PU.1 using an in vitro “stress-test” based on repetitive challenge with CAR cognate CEA+ cancer cells.”

  • The paper relies on this without support.

    The CEA+ BxPC-3 pancreatic cancer cell model is representative of solid tumors for CAR T cell therapy.

    “CEA-positive human pancreatic cancer cells BxPC-3 (ATCC CRL-1420) served as target cells [16].”
3 of 3

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Cited works that were retracted

Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.

  • Cites a retracted work: 10.1186/s13287-022-02819-x

    Info

    The cited work was retracted on 2026-06-10 (notice 10.1186/s13287-026-05046-w), not before this paper was published (2024-08-01).

    Cited work 10.1186/s13287-022-02819-x · retracted 2026-06-10 · notice 10.1186/s13287-026-05046-w · this paper published 2024-08-01

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Related

Authors
Harrer, D. C., Eder, M., Barden, M., Pan, H., Herr, W., & Abken, H.
Affiliations
  • University Hospital Regensburg (DE)
  • Leibniz Institute for Immunotherapy
Corresponding author
Harrer, Dennis Christoph
ORCID
Venue
Cancers
Publisher
MDPI AG
Published
2024-08-01
Volume
16
Issue
15
Pages
2737
ISSN
2072-6694 (ISSN-L)
DOI
10.3390/cancers16152737
PMC
PMC11311516
OpenAlex
W4401212939
Semantic Scholar
4e2e64143733efe6284404a57c5345363d850229
Cited by
1
References
28
Citations by year
2025: 1
FWCI
0.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancers (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • University of Regensburg Publication Server (University of Regensburg)
Funders
  • Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (324392634—TRR221)
  • Else-Kröner Fresenius Foundation (324392634—TRR221)
  • Bavarian Cancer Research Center (BZKF) BZKF-Young Scientist Fellowship (324392634—TRR221)
Topics
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
PU.1, chimeric antigen receptor T cells, CAR T-cell therapy, interferon-beta, innate-like T cells, 4-1BB, IL-2 production, CAR T cell persistence, solid tumor immunotherapy, T cell activation, CD40, CD80, CD86, CD70

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