New Molecular and Computational Approaches to Study Immune and Metabolic Interactions in Cancer Biology

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Methods".

Deadline for manuscript submissions: closed (25 July 2025) | Viewed by 1360

Special Issue Editors


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Guest Editor
1. Humanitas Clinical and Research Center–IRCCS, Rozzano, Italy
2. Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
Interests: tumor-microenvironment; cancer immunity; macrophages; immunometabolism

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Guest Editor
Humanitas Clinical and Research Center– IRCCS, Rozzano, Italy
Interests: inflammation; immunology; brain homeostasis and disease; macrophages

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Guest Editor
1. Humanitas Clinical and Research Center–IRCCS, Rozzano, Italy
2. Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
Interests: digital-pathology; immunoncology; computational imaging analysis; artificial intelligence

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Guest Editor
1. Humanitas Clinical and Research Center–IRCCS, Rozzano, Italy
2. Milan Unit, Istituto di Ricerca Genetica e Biomedica (IRGB), National Research Council, Milan, Italy
Interests: cancer metabolism; solid and liquid cancer; cancer stem cells; tumor inflammation
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Special Issue Information

Dear Colleagues,

Cancer, together with cardiovascular diseases, represents one of the main causes of death worldwide, with healthcare costs estimated at billions of euros every year. For all these reasons, fighting cancer has been one of the biggest challenges for medical research in the last century.
Cancer research is committed to meeting this huge medical need by proposing new experimental and computational approaches integrating different research fields in order to identify promising features to be used to detect, prevent, and treat cancer, the four objectives around which cancer research is built. Therefore, the integration of multiple points of view can be used to better describe and characterize the complex tumor biology.

Studies on cancer metabolism, arising from Warburg's theory, have exponentially grown in recent decades and currently represent one of the main hallmarks of cancer. Recently, on the basis of the “Seed and Soil” theory proposed by Paget, there have been numerous research papers studying the complex metabolic symbiotic relationship between the microenvironment and tumor cells. In fact, it is now widely acknowledged that the tumor microenvironment plays an important role in tumor progression as well as in responses to therapies, which determine patient survival. In this context, immune cells are deeply investigated, and the amounts and types, commonly referred to as the immune landscape, have been robustly underlined to have prognostic value based on the evidence showing that specific cell types are associated with distinct disease outcomes in patients.

Integration of multiple research fields is nowadays helped by artificial intelligence (AI) and digital pathology, which are gaining interest in cancer research since they allow to streamline and ameliorate diagnostic and prognostic processes. The deep learning models that are being built can extract features from huge and various datasets (AI) or from images (digital pathology) even beyond the visual perception, with the ultimate aim of improving disease detection, prevention, and treatment.

Original research articles and reviews on such research fields, as well as the integration of those that represent a step forward in understanding the complex molecular biology of cancer are welcome.

Dr. Federica Mornata
Dr. Luca De Feo
Dr. Rebecca Polidori
Dr. Matteo Brindisi
Guest Editors

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Keywords

  • solid and liquid cancer
  • cancer metabolism
  • tumor microenvironment
  • digital pathology
  • immunoncology

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Published Papers (1 paper)

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20 pages, 3954 KB  
Article
Interpretation of the Transcriptome-Based Signature of Tumor-Initiating Cells, the Core of Cancer Development, and the Construction of a Machine Learning-Based Classifier
by Seung-Hyun Jeong, Jong-Jin Kim, Ji-Hun Jang and Young-Tae Chang
Cells 2025, 14(16), 1255; https://doi.org/10.3390/cells14161255 - 14 Aug 2025
Viewed by 896
Abstract
Tumor-initiating cells (TICs) constitute a subpopulation of cancer cells with stem-like properties contributing to tumorigenesis, progression, recurrence, and therapeutic resistance. Despite their biological importance, their molecular signatures that distinguish them from non-TICs remain incompletely characterized. This study aimed to comprehensively analyze transcriptomic differences [...] Read more.
Tumor-initiating cells (TICs) constitute a subpopulation of cancer cells with stem-like properties contributing to tumorigenesis, progression, recurrence, and therapeutic resistance. Despite their biological importance, their molecular signatures that distinguish them from non-TICs remain incompletely characterized. This study aimed to comprehensively analyze transcriptomic differences between TICs and non-TICs, identify TIC-specific gene expression patterns, and construct a machine learning-based classifier that could accurately predict TIC status. RNA sequencing data were obtained from four human cell lines representing TIC (TS10 and TS32) and non-TIC (32A and Epi). Transcriptomic profiles were analyzed via principal component, hierarchical clustering, and differential expression analysis. Gene-Ontology and Kyoto-Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted for functional interpretation. A logistic-regression model was trained on differentially expressed genes to predict TIC status. Model performance was validated using synthetic data and external projection. TICs exhibited distinct transcriptomic signatures, including enrichment of non-coding RNAs (e.g., MIR4737 and SNORD19) and selective upregulation of metabolic transporters (e.g., SLC25A1, SLC16A1, and FASN). Functional pathway analysis revealed TIC-specific activation of oxidative phosphorylation, PI3K-Akt signaling, and ribosome-related processes. The logistic-regression model achieved perfect classification (area under the curve of 1.00), and its key features indicated metabolic and translational reprogramming unique to TICs. Transcriptomic state-space embedding analysis suggested reversible transitions between TIC and non-TIC states driven by transcriptional and epigenetic regulators. This study reveals a unique transcriptomic landscape defining TICs and establishes a highly accurate machine learning-based TIC classifier. These findings enhance our understanding of TIC biology and show promising strategies for TIC-targeted diagnostics and therapeutic interventions. Full article
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