Cancer and Immune System Interactions

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

Deadline for manuscript submissions: 20 July 2026 | Viewed by 1267

Special Issue Editors


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Guest Editor
Department of Surgery, The University of Melbourne, Parkville 3050, Australia
Interests: cytokine/growth factor signalling; cancer biology; exosomes; cancer immunology
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Basic Sciences, Kansas City University, Joplin, MO, USA
Interests: cell signaling; nuclear receptors; cancer biology; cell biology

Special Issue Information

Dear Colleagues,

Cancer and immune system interactions play a crucial role in shaping tumor development and progression. The immune system continuously interacts with cancer cells, not only detecting and eliminating malignant cells but also, under certain conditions, supporting tumor growth, immune evasion, and resistance to therapy. Understanding how these immune responses are modulated within the tumor microenvironment is critical to developing new strategies for cancer prevention, diagnosis, and treatment.

This Special Issue invites original research and reviews that explore the diverse roles of the immune system in cancer biology. We welcome studies investigating immune surveillance, inflammation-driven tumor initiation and progression, and the mechanisms that regulate immune activity within the tumor microenvironment. Submissions focused on immune-based therapies—such as checkpoint inhibitors, adoptive cell transfer, cancer vaccines, or novel immunomodulatory agents—are also strongly encouraged, particularly those that shed light on mechanisms of response, resistance, or therapeutic synergy. Of particular interest are findings that reveal novel signaling pathway interactions, immune cell states, tumor-intrinsic modulators, or environmental factors that influence immune engagement and clinical outcomes.

Submissions spanning cancer types, model systems, and experimental approaches are encouraged. We aim to highlight work that connects molecular mechanisms with translational insight and reflects the breadth of emerging science in this field.

Dr. Hong-Jian Zhu
Dr. Bradley Creamer
Guest Editors

Manuscript Submission Information

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Keywords

  • cancer immunology
  • tumor microenvironment
  • immune evasion
  • immunotherapy
  • tumor–immune interactions
  • immune checkpoint regulation
  • translational oncology

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Published Papers (2 papers)

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Research

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19 pages, 2204 KB  
Article
Immune Cell-Specific and Isoform-Selective Regulation of CD44 in Pancreatic Ductal Adenocarcinoma Links Lymph Node Variant Loss and Exosomal CD44 to Clinical Outcome in Pancreatic Ductal Adenocarcinoma
by Alara Karabiber, Yong Zhou, Anke Mittelstädt, Frederik Johannes Hansen, Melanie Litau, Isabelle Kuchenreuther, Johanne Mazurie, Finn Niklas Clausen, Sebastian Klöckner, Franziska Czubayko, Nadine Weisel, Bettina Klösch, Talida Andert-Veres, Stefanie Kröber, Susanne Merkel, Andreas R. R. Weiss, Maximilian Brunner, Christian Krautz, Robert Grützmann, Georg F. Weber and Paul Davidadd Show full author list remove Hide full author list
Cells 2026, 15(5), 411; https://doi.org/10.3390/cells15050411 - 27 Feb 2026
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Abstract
Pancreatic ductal adenocarcinoma (PDAC) is characterized by immune cell dysfunction and poor prognosis. CD44, a cell surface glycoprotein with multiple splice variants, has been implicated in tumor progression, but its compartment-specific roles in PDAC remain unclear. CD44 standard and variant isoform expression was [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) is characterized by immune cell dysfunction and poor prognosis. CD44, a cell surface glycoprotein with multiple splice variants, has been implicated in tumor progression, but its compartment-specific roles in PDAC remain unclear. CD44 standard and variant isoform expression was analyzed in patient-derived lymph nodes (LNs) by quantitative PCR. Immune cell-specific CD44 expression was assessed by flow cytometry in LNs and peripheral blood. Soluble and exosome-associated CD44 (exo-CD44) were measured in plasma. Clinical associations and survival analyses were performed. Transcriptomic, immune infiltration, immune checkpoint, and drug sensitivity analyses were conducted using TCGA-PAAD and pharmacogenomic datasets. CD44 standard isoform expression was unchanged in PDAC LNs, whereas multiple CD44 variant isoforms (v4–v10) were significantly reduced and associated with metastatic disease and poor survival, particularly CD44v5, v6, v7, and v10. CD44 expression was enriched in CD45+ immune cells, with highest levels in CD4+ T cells in both LNs and blood. Soluble CD44 levels showed no clinical associations. In contrast, exo-CD44 levels were reduced overall in PDAC but increased in patients with distant metastasis, positive resection margins, systemic inflammation, and reduced survival. High CD44 expression was associated with advanced disease, immune cell infiltration, immune checkpoint gene expression, reduced sensitivity to gemcitabine, paclitaxel, rapamycin, and FMK, and distinct CTLA4/PD-L1 checkpoint profiles. CD44 exhibits compartment-specific regulation in PDAC, linking immune remodeling, exosome signaling, and therapeutic resistance to adverse clinical outcome. Full article
(This article belongs to the Special Issue Cancer and Immune System Interactions)
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Review

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19 pages, 2176 KB  
Review
Natural Products Targeting Angiogenesis and Tumor Microenvironment in Gastrointestinal Malignancies
by Idris Arslan
Cells 2026, 15(7), 623; https://doi.org/10.3390/cells15070623 - 31 Mar 2026
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Abstract
Gastrointestinal malignancies remain among the leading causes of cancer-related morbidity and mortality worldwide, largely due to late diagnosis, aggressive tumor progression, and resistance to conventional therapies. Tumor angiogenesis and the tumor microenvironment (TME) play crucial roles in the initiation, growth, and metastatic dissemination [...] Read more.
Gastrointestinal malignancies remain among the leading causes of cancer-related morbidity and mortality worldwide, largely due to late diagnosis, aggressive tumor progression, and resistance to conventional therapies. Tumor angiogenesis and the tumor microenvironment (TME) play crucial roles in the initiation, growth, and metastatic dissemination of gastrointestinal cancers. Hypoxia-driven signaling pathways, including hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and inflammatory mediators such as NF-κB and MAPK, are key regulators of these processes. Increasing evidence suggests that natural products derived from medicinal plants and other biological sources may modulate these pathways and exhibit anti-angiogenic, anti-inflammatory, and anti-fibrotic properties. This review summarizes recent findings on natural compounds that influence angiogenesis and tumor microenvironment dynamics through the regulation of molecular pathways involved in hypoxia signaling, extracellular matrix remodeling, fibroblast activation, and inflammatory responses. Compounds such as neotuberostemonine, aloperine, silymarin derivatives, tanshinone IIA, berberine, asiatic acid, and phloretin demonstrate promising biological activities in experimental models by targeting pathways including HIF-1α, PI3K/AKT/mTOR, TGF-β/Smad, and NF-κB signaling. However, further studies focusing on gastrointestinal cancer models and clinical validation are required to translate these preclinical observations into effective therapeutic strategies. Full article
(This article belongs to the Special Issue Cancer and Immune System Interactions)
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