Recent Advances in Tumor Microenvironment Biology

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Cancer Biology".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 3652

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Department of Pharmaceutical and Biomedical Sciences, California Northstate University College of Pharmacy, Elk Grove, CA 95757, USA
Interests: innate immunity of complement system in sepsis, cancer, and diabetes; signal transduction of protein kinase C (PKC) signaling in cancer initiation, development, and metastasis; small G protein Rac1 in cancer transformation and metastasis

Special Issue Information

Dear Colleagues,

Recent advances in tumor microenvironment (TME) biology have revolutionized our understanding of cancer progression, metastasis, and treatment response. The tumor microenvironment, once considered merely a supportive backdrop for cancer cells, is now recognized as a dynamic ecosystem comprising various cell types, extracellular matrix components, and signaling molecules that profoundly influence tumor behavior.

One of the most significant breakthroughs in TME research has been the identification and characterization of different cellular components within the microenvironment. Stromal cells such as cancer-associated fibroblasts (CAFs), immune cells including T cells, B cells, macrophages, and myeloid-derived suppressor cells (MDSCs), as well as endothelial cells, collectively shape the TME's complexity. Understanding the intricate crosstalk among these cells and their interactions with cancer cells has provided critical insights into tumor development and progression.

Moreover, recent studies have shed light on the role of the extracellular matrix (ECM) in TME dynamics. The ECM, consisting of various proteins and polysaccharides, not only provides structural support but also serves as a reservoir for growth factors and cytokines that regulate tumor cell behavior. Alterations in ECM composition and stiffness have been implicated in tumor invasion, angiogenesis, and immune evasion, highlighting the importance of ECM remodeling in cancer biology.

Advancements in single-cell analysis techniques have enabled researchers to dissect the heterogeneity within the TME at unprecedented resolution. By profiling individual cells within tumors, scientists have uncovered distinct subpopulations with unique functional properties and gene expression signatures. This granularity has facilitated the identification of novel therapeutic targets and biomarkers for predicting treatment response and patient outcomes.

Furthermore, the emerging field of immunotherapy has transformed cancer treatment paradigms by harnessing the power of the immune system to target and eliminate tumors. Checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapy, and immune checkpoint blockade have demonstrated remarkable efficacy in a subset of patients across various cancer types. Understanding the complex interplay between tumors and the immune microenvironment is essential for optimizing immunotherapeutic strategies and overcoming resistance mechanisms.

In conclusion, recent advances in tumor microenvironment biology have deepened our understanding of cancer biology and opened up new avenues for therapeutic intervention. By elucidating the intricate cellular and molecular interactions within the TME, researchers aim to develop more effective and personalized treatments that target not only cancer cells but also their supportive microenvironment. As we continue to unravel the complexities of the TME, we move closer to realizing the promise of precision medicine in the fight against cancer.

Dr. Hongbin Wang
Guest Editor

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Keywords

  • tumor microenvironment
  • immune cells’ stromal cells
  • extracellular matrix
  • angiogenesis
  • metabolic reprogramming
  • tumor-associated macrophages
  • tumor-infiltrating lymphocytes
  • cytokine signaling
  • therapeutic targeting strategies
 

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Published Papers (2 papers)

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Research

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Article
RAW264.7 Macrophages as a Polarization Model in the Context of Pancreatic Cancer and Chemokine Release
by Aydar Khabipov, Lea Miebach, Maik Lenz, Stephan Kersting and Sander Bekeschus
Biology 2025, 14(4), 320; https://doi.org/10.3390/biology14040320 - 21 Mar 2025
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Abstract
The TME is a critical niche for determining the fate of cancer therapy. Tumor cells often polarize nontumor cells, including immune cells, in the TME to favor cancer growth. In pancreatic cancer, macrophages are associated with poor therapy outcomes and unfavorable survival, especially [...] Read more.
The TME is a critical niche for determining the fate of cancer therapy. Tumor cells often polarize nontumor cells, including immune cells, in the TME to favor cancer growth. In pancreatic cancer, macrophages are associated with poor therapy outcomes and unfavorable survival, especially when rendered into M2 macrophages. The latter show features also found in so-called tumor-associated macrophages (TAM), which are described as protecting and propelling tumor growth. In this context, it has been understudied which pancreatic cancer chemokines contribute to macrophage polarization. To this end, we analyzed murine RAW264.7 macrophages and Panc02 and PDA6606 pancreatic cancer cells in mono- and coculture to identify release patterns of 13 chemokines. Artificial macrophage polarization confirmed prominent changes in surface receptor and chemokine secretion profiles. Strikingly, RAW264.7 cocultures with Panc02 or PDA6606 were congruent in showing elevated levels of CCL2, CCL5, CCL17, CCL20, CCL22, CXCL5, and CXCL10. Further underlining the suitability of our in vitro model, both pancreatic cancer cell lines showed similar modulation of the critical macrophage polarization markers arginase, CD206, and iNOS, as well as chemokine receptors CCR2 and CCR4. Collectively, we demonstrated that our model is suitable for testing the roles and functions of chemokines in macrophage polarization by pancreatic cancer cells. Full article
(This article belongs to the Special Issue Recent Advances in Tumor Microenvironment Biology)
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Review

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38 pages, 20523 KiB  
Review
Unveiling the Tumor Microenvironment Through Fibroblast Activation Protein Targeting in Diagnostic Nuclear Medicine: A Didactic Review on Biological Rationales and Key Imaging Agents
by Juliette Fouillet, Jade Torchio, Léa Rubira and Cyril Fersing
Biology 2024, 13(12), 967; https://doi.org/10.3390/biology13120967 - 24 Nov 2024
Cited by 1 | Viewed by 2626
Abstract
The tumor microenvironment (TME) is a dynamic and complex medium that plays a central role in cancer progression, metastasis, and treatment resistance. Among the key elements of the TME, cancer-associated fibroblasts (CAFs) are particularly important for their ability to remodel the extracellular matrix, [...] Read more.
The tumor microenvironment (TME) is a dynamic and complex medium that plays a central role in cancer progression, metastasis, and treatment resistance. Among the key elements of the TME, cancer-associated fibroblasts (CAFs) are particularly important for their ability to remodel the extracellular matrix, promote angiogenesis, and suppress anti-tumor immune responses. Fibroblast activation protein (FAP), predominantly expressed by CAFs, has emerged as a promising target in both cancer diagnostics and therapeutics. In nuclear medicine, targeting FAP offers new opportunities for non-invasive imaging using radiolabeled fibroblast activation protein inhibitors (FAPIs). These FAP-specific radiotracers have demonstrated excellent tumor detection properties compared to traditional radiopharmaceuticals such as [18F]FDG, especially in cancers with low metabolic activity, like liver and biliary tract tumors. The most recent FAPI derivatives not only enhance the accuracy of positron emission tomography (PET) imaging but also hold potential for theranostic applications by delivering targeted radionuclide therapies. This review examines the biological underpinnings of FAP in the TME, the design of FAPI-based imaging agents, and their evolving role in cancer diagnostics, highlighting the potential of FAP as a target for precision oncology. Full article
(This article belongs to the Special Issue Recent Advances in Tumor Microenvironment Biology)
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