Evidence map›Paper›PMID 39868284›Full record

ArticlebioRxiv : the preprint server for biology2025

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, Lea W Rysavy, Leon Su, Ossama Labiad, Stefano Testa, Heather Ogana, Deepa Waghray and 7 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Hua JiangDepartment of Radiation Oncology, 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.
Aastha PalDepartment 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.
Leon SuDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine. Stanford, CA, 94305, USA.
Ossama LabiadDepartment 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.
Gay M CrooksDepartment of Pathology & Laboratory Medicine, 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.
K Christopher GarciaDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine. Stanford, CA, 94305, USA.
Anusha KalbasiDepartment of Radiation Oncology, Stanford University School of Medicine. Stanford, CA, 94305, USA.

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

Arming T cells with a synthetically orthogonal IL-9 receptor (o9R) permits facile engraftment and potent anti-tumor functions. We considered whether the paucity of natural IL-9R expression could be exploited for T cell immunotherapy given that, in mice, high doses of IL-9 were well-tolerated without discernible immune modulation. Compared to o9R, T cells engineered with IL-9R exhibit superior tissue infiltration, stemness, and anti-tumor activity. These qualities are consistent with a stronger JAK/STAT signal, which in addition to STAT1/3/5, unexpectedly includes STAT4 (canonically associated with IL-12 but not common γ-chain cytokines). IL-9R T cells are exquisitely sensitive to perturbations of proximal signaling, including structure-guided attenuation, amplification, and rebalancing of JAK/STAT signals. Biased IL-9R mutants uncover STAT1 as a rheostat between proliferative stem-like and terminally differentiated effector states. In summary, we identify native IL-9/IL-9R as a natural cytokine-receptor pair with near-orthogonal qualities and an optimal JAK/STAT signaling profile for engineered T cell therapy.

Identifiers

PMID39868284
PMCPMC11760723

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.