Evidence map›Paper›PMID 42374407›Full record

ArticleBMC medicine2026

Engineered iMSCs delivering wild-type IL-2 achieve dose-sparing tumor control via CD25-dependent CD8

Shuqing Tang, Mengting Han, Peiyun Wang, Fan Lu, Ying Zhang, Zhixing Li, Shenglan Zhou, Yusang Zhang, Zujia Wang, Junya Zhao and 6 more

Abstract read
In one paragraph

Article in BMC medicine, 2026. 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

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Shuqing Tang *Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, China.
Mengting Han *Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, China.
Peiyun WangCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, China.
Fan LuCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, China.
Ying ZhangCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, China.
Zhixing LiCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, China.
Shenglan ZhouCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, China.
Yusang ZhangCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, China.
Zujia WangLakeshore Biotech Co., Ltd, Shanghai, 201208, China.
Junya ZhaoLakeshore Biotech Co., Ltd, Shanghai, 201208, China.
Yuquan LuoCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, China.
Zhixin TianCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, China.
Mai FengHunan Key Laboratory of Animal Models for Human Diseases, School of Life Sciences, Central South University, Changsha, 410078, China.
Guanshan ZhuLakeshore Biotech Co., Ltd, Shanghai, 201208, China.
Lingqian WuCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, China. wulingqian@sklmg.edu.cn.
Desheng LiangCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, China. liangdesheng@sklmg.edu.cn.ORCID 0000-0002-9451-8585

Funding

the National Key Research and Development Program of China 2022YFC2703402the National Natural Science Foundation of China 82271752
6 · The paper itself

Abstract

backgroundInterleukin-2 (IL-2), the first FDA-approved cytokine-based immunotherapy, can induce durable antitumor responses but its broader use is curtailed by life-threatening, dose-dependent toxicities. This narrow therapeutic window has limited clinical translation for decades. Genetically engineered mesenchymal stromal cells (MSCs) have emerged as attractive IL-2 delivery vehicles due to their low immunogenicity and intrinsic tumor-homing capacity.

methodsHuman induced pluripotent stem cells (iPSCs) were edited by CRISPR/Cas9 to knock in wild-type IL-2 (wtIL-2) or a receptor-biased variant (IL-2v) into the B2M or B3 safe-harbor loci, generating cytokine-secreting iPSC-derived MSCs (iMSCs). Antitumor activity was evaluated in co-cultures of iMSCs, tumor cells, and peripheral blood mononuclear cells (PBMCs) by flow cytometry. In vivo, systemically administered iMSCs were tracked by live imaging in mice bearing subcutaneous tumors to assess biodistribution and tumor targeting. Tumor control was monitored by longitudinal tumor growth and end-point volume; toxicity was evaluated by lung wet weight and blood biochemistry. Immune cell states within the tumor microenvironment were characterized by flow cytometry and RNA sequencing. Data (mean ± s.e.m.) were analyzed in GraphPad Prism using t-tests, ANOVA, or Kruskal-Wallis tests, as appropriate (n = biological replicates; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001).

resultsSurprisingly, we found that under low-dose conditions, only iMSCs with IL-2 overexpression-but not unmodified iMSCs or free IL-2 alone-induced robust upregulation of CD25 on CD8

conclusionsThese findings point to a mechanism by which iMSC-delivered IL-2 reshapes the tumor microenvironment through CD25-dependent CD8⁺ T-cell activation. Furthermore, the results support the concept that this platform enables a more dose-efficient cytokine delivery strategy with an improved safety profile, thereby facilitating the clinical translation of off-the-shelf allogeneic iMSC-based gene therapies.

Indexed as

CD8-Positive T-LymphocytesInduced Pluripotent Stem CellsInterleukin-2Interleukin-2 Receptor alpha SubunitLymphocyte ActivationMesenchymal Stem CellsNeoplasmsAnimalsCell Line, TumorFemaleHumansImmunotherapyMiceIL2RA protein, humanInterleukin-2Interleukin-2 Receptor alpha SubunitCD25 signalingEngineered iMSCsTargeted deliveryTumor immunotherapyWild-type IL-2

Identifiers

PMID42374407
PMCPMC13579723

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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.