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Advanced Research in Immune Cell Therapy
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Advanced Research in Immune Cell Therapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (20 February 2026) | Viewed by 530

Special Issue Editor

Dr. Alexander Huang

E-Mail Website
Guest Editor
Department of MD Education, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Interests: molecular biology; machine learning; SHAP (explainable AI); medical informatics; biomedical research

Special Issue Information

Dear Colleagues,

This Special Issue is dedicated to showcasing cutting-edge advances in molecular research. We invite contributions that illuminate the underlying molecular mechanisms governing biological processes, highlighting the latest developments in molecular biology, genomics, proteomics, and bioinformatics. By bridging innovative experimental techniques with computational approaches, this issue aims to advance our understanding of cellular signaling, gene regulation, and molecular interactions. Submissions addressing novel diagnostic and therapeutic strategies that leverage molecular insights are especially encouraged, as they have the potential to transform personalized medicine and improve patient outcomes. In addition, we welcome reviews and methodological papers that provide comprehensive overviews and critical evaluations of emerging trends in molecular research. Our goal is to foster an interdisciplinary dialog that connects molecular science with broader biomedical applications, ultimately contributing to the development of more effective interventions and a deeper understanding of the molecular basis of health and disease.

Dr. Alexander Huang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • molecular biology
  • bioinformatics
  • proteomics
  • molecular mechanisms
  • genomics

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Published Papers (1 paper)

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Research

15 pages, 1311 KB  
Article
Extracellular ATP Functions as a Metabolic Lineage Selection Signal That Stabilizes Tc9 Cells During Adoptive T Cell Therapy
by Jie Ren, Zhengrong Gong, Yutong Zhong, Ruipei Xiao, Khadija Urooj, Yuan Gao, Enguang Bi and Handuo Wang
Int. J. Mol. Sci. 2026, 27(7), 3169; https://doi.org/10.3390/ijms27073169 - 31 Mar 2026
Viewed by 260
Abstract
Adoptive T cell therapy (ACT) remains limited in solid tumors by poor T cell persistence within the metabolically hostile tumor microenvironment (TME). Although IL-9-producing CD8+ T cells (Tc9) consistently demonstrate superior antitumor efficacy compared with conventional Tc1 cells, the selective pressures that [...] Read more.
Adoptive T cell therapy (ACT) remains limited in solid tumors by poor T cell persistence within the metabolically hostile tumor microenvironment (TME). Although IL-9-producing CD8+ T cells (Tc9) consistently demonstrate superior antitumor efficacy compared with conventional Tc1 cells, the selective pressures that shape their functional advantage remain unclear. Here, we show that effective ACT-mediated tumor control is accompanied by a marked increase in intratumoral extracellular ATP (eATP), representing a common metabolic consequence of tumor cell destruction. Despite comparable ATP accumulation following Tc1 or Tc9 treatment, these subsets exhibit strikingly distinct responses to ATP stress. Tc1 cells are highly susceptible to ATP-induced apoptosis, whereas Tc9 cells display intrinsic resistance, resulting in superior in vivo persistence. Mechanistically, Tc9 cells actively convert ATP signaling into enhanced mitochondrial fitness, characterized by increased oxidative phosphorylation and spare respiratory capacity. ATP exposure further drives Tc9 cells toward a tissue-resident memory (TRM) phenotype through activation of the TGF-β signaling axis. Transcriptomic and molecular analyses reveal that purinergic signaling pathways, including elevated expression of the ATP receptor P2RX7, are intrinsically enriched in Tc9 cells and are further amplified upon ATP stimulation. Collectively, our findings identify extracellular ATP as a metabolic lineage selection signal in ACT, demonstrating that ATP stress preferentially stabilizes metabolically resilient Tc9 cells by linking purinergic sensing to mitochondrial remodeling and TRM programming, thereby providing a conceptual basis for enhancing the persistence and efficacy of engineered T cell therapies in solid tumors. Full article
(This article belongs to the Special Issue Advanced Research in Immune Cell Therapy)
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