Evidence map›Paper›PMID 41274289›Full record

ArticleImmunity2026

IL-9 as a naturally orthogonal cytokine with optimal JAK/STAT signaling for engineered T cell therapy.

Hua Jiang, Sam Limsuwannarot, Kayla R Kulhanek, Aastha Pal, Ossama Labiad, Lea W Rysavy, Ada Wong, Leon Su, Sarah Cavender, Johnathon Soro and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Immunity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Hua JiangDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA; Departments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sam LimsuwannarotDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Kayla R KulhanekDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Medical Scientist Training Program, Stanford University School of Medicine, Stanford, CA 94143, USA; Stanford Center for Cancer Cell Therapy, Stanford University School of Medicine, Stanford, CA 94143, USA.
Aastha PalDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ossama LabiadDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lea W RysavyDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Ada WongDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Leon SuDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Sarah CavenderDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Johnathon SoroDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Stefano TestaDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Heather OganaDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Deepa WaghrayDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Pingdong TaoDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Kevin M JudeDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Christopher S SeetBroad Stem Cell Research Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Medicine, Division of Hematology-Oncology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Gay M CrooksDepartment of Pathology & Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Broad Stem Cell Research Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Division of Pediatric Hematology-Oncology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Everett J ModingDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94143, USA.
K Christopher GarciaDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Parker Institute for Cancer Immunotherapy, 1 Letterman Drive, Suite D3500, San Francisco, CA 94129, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Anusha KalbasiDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Center for Cancer Cell Therapy, Stanford University School of Medicine, Stanford, CA 94143, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94143, USA. Electronic address: akalbasi@stanford.edu.

Funding

Supplement for Google cloud build-outR24GM137786 · NIGMS · UNIV OF ARKANSAS FOR MED SCIS · PI Alan Tackett · 2020 to 2026
$15.4M
Structure-based engineering of immune cytokine signalingR01AI051321 · NIAID · STANFORD UNIVERSITY · PI Kenan Christopher GARCIA · 2002 to 2026
$5.6M
Synthetic IL9R signaling to rewire T cells for adoptive cell therapy of cancerR37CA273074 · NCI · STANFORD UNIVERSITY · PI Anusha Kalbasi · 2022 to 2026
$1.8M
Targeting Radiation-Induced Myeloid Cells to Promote T cell Immunity in Undifferentiated Pleomorphic SarcomaK08CA245181 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KALBASI, ANUSHA · 2020 to 2025
$1.1M
30-parameter FACSymphony A3 flow cytometer for Shared Resource LabS10OD026831 · OD · STANFORD UNIVERSITY · PI NOLAN, GARRY P · 2019 to 2019
$510k
NCI NIH HHS K08 CA245181NCI NIH HHS R37 CA273074NIAID NIH HHS R01 AI051321NIGMS NIH HHS R24 GM137786NIH HHS S10 OD026831
6 · The paper itself

Abstract

Cytokines and their receptors enable precise tuning of T cell function. Leveraging this biology holds tremendous promise for optimizing antitumor immunity. Arming T cells with a synthetically orthogonal interleukin (IL)-9 receptor (o9R), for instance, permits facile engraftment and potent anti-tumor functions. Exploiting the paucity of wild-type IL-9R expression and the safety of high doses of IL-9, here, we showed that, compared with o9R, T cells engineered with wild-type IL-9R exhibited superior tissue infiltration, stemness, and anti-tumor activity. These qualities were consistent with a stronger Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signal, which included canonically IL-12-driven STAT4 in addition to STAT1/3/5. IL-9R T cells were exquisitely sensitive to perturbations of proximal signaling, including structure-guided attenuation, amplification, and rebalancing of JAK/STAT signals. Biased IL-9R mutants showed that STAT1 acts as a rheostat between stem-like and effector states. In summary, we identify IL-9/IL-9R as a naturally orthogonal cytokine-receptor pair with an optimal JAK/STAT signaling profile for engineered T cell therapy.

Indexed as

Immunotherapy, AdoptiveInterleukin-9Janus KinasesSTAT Transcription FactorsT-LymphocytesAnimalsHumansMiceReceptors, Interleukin-9Signal TransductionInterleukin-9Janus KinasesReceptors, Interleukin-9STAT Transcription Factorsadoptive T cell therapycancer immunotherapyCAR T cell therapycell signalingcommon gamma chaincytokinesIL-9IL-9RJAK/STATTCR T cell therapy

Identifiers

PMID41274289
PMCPMC12643178

What OpenQuestion holds

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Registered trials

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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.