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Cancers
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The Tumor Microenvironment: Interplay Between Immune Cells
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The Tumor Microenvironment: Interplay Between Immune Cells

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 2477

Special Issue Editors

Dr. Jared Rowe

E-Mail Website
Guest Editor
Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02109, USA
Interests: tumor immune microenvironment; immune metabolism; pediatric cancer
Dr. Kristen E. Pauken

E-Mail Website
Guest Editor
Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: tumor immune microenvironment; PD-1 immunotherapy; CD8+ T cells; T cell exhaustion; immune-related adverse events; autoimmunity; melanoma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The immune system provides critical defense against tumors. While therapies aimed at immune cells have proven efficacious across multiple cancer types, many patients either fail to respond or relapse. Overcoming the impairment of immune cells within the tumor microenvironment (TME) could improve outcomes for patients receiving immune therapies.

For this Special Issue, original research articles and reviews regarding the interplay between immune cells within the TME are welcome. Research areas may include (but not limited to) the following: immune mechanisms of resistance, interplay between cancer and immune cells and novel combination strategies. We look forward to receiving your contributions.

Dr. Jared Rowe
Dr. Kristen E. Pauken
Guest Editors

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 communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • tumor immune microenvironment
  • metabolic microenvironment
  • immune cells

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Published Papers (3 papers)

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Research

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30 pages, 7745 KiB  
Article
Single-Cell Profiling Reveals Global Immune Responses During the Progression of Murine Epidermal Neoplasms
by Xiying Fan, Tonya M. Brunetti, Kelsey Jackson and Dennis R. Roop
Cancers 2025, 17(8), 1379; https://doi.org/10.3390/cancers17081379 - 21 Apr 2025
Viewed by 355
Abstract
Background/Objectives: Immune cells determine the role of the tumor microenvironment during tumor progression, either suppressing tumor formation or promoting tumorigenesis. This study aimed to fully characterize immune cell responses during skin tumor progression. Methods: Using single-cell RNA sequencing, we analyzed the profile of [...] Read more.
Background/Objectives: Immune cells determine the role of the tumor microenvironment during tumor progression, either suppressing tumor formation or promoting tumorigenesis. This study aimed to fully characterize immune cell responses during skin tumor progression. Methods: Using single-cell RNA sequencing, we analyzed the profile of immune cells in the tumor microenvironment of control mouse skins and skin tumors at the single-cell level. Results: We identified 15 CD45+ immune cell clusters, which broadly represent the most functionally characterized immune cell types including macrophages, Langerhans cells (LC), conventional type 1 dendritic cells (cDC1), conventional type 2 dendritic cells (cDC2), migratory/mature dendritic cells (mDC), dendritic epidermal T cells (DETC), dermal γδ T cells (γδT), T cells, regulatory T cells (Tregs), natural killer cells (NK), type 2 innate lymphoid cells (ILC2), neutrophils (Neu), mast cells (Mast), and two proliferating populations (Prolif.1 and Prolif.2). Skin tumor progression reprogramed immune cells and led to a marked increase in the relative percentages of macrophages, cDC2, mDC, Tregs, and Neu. Macrophages, the largest cell cluster of immune cells in skin tumors. In addition, macrophages emerged as the predominant communication ‘hub’ in skin tumors, highlighting the importance of macrophages during skin tumor progression. In contrast, other immune cell clusters decreased during skin tumor progression, including DETC, γδT, ILC2, and LC. In addition, skin tumor progression dramatically upregulated Jak2/Stat3 expression and the interferon response across various immune cell clusters. Further, skin tumor progression activated T cells and NK cells indicated by elevated expression of IFN-γ and Granzyme B in skin tumors. Meanwhile, a pronounced infiltration of M2-macrophages and Tregs in skin tumors created an immunosuppressive microenvironment, consistent with the elevated expression of the Stat3 pathway in skin tumors. Conclusions: Our study elucidates the immune cell landscape of epidermal neoplasms, offering a comprehensive understanding of the immune response during skin tumor progression and providing new insights into cancer immune evasion mechanisms. Full article
(This article belongs to the Special Issue The Tumor Microenvironment: Interplay Between Immune Cells)
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Review

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29 pages, 1945 KiB  
Review
Immune Cell Interplay in the Fight Against GBM
by Nico Vallieri and Angeliki Datsi
Cancers 2025, 17(5), 817; https://doi.org/10.3390/cancers17050817 - 26 Feb 2025
Viewed by 797
Abstract
Despite multimodal therapies, the treatment of glioblastoma remains challenging. In addition to the very complex mechanisms of cancer cells, including specialized phenotypes that enable them to proliferate, invade tissues, and evade immunosurveillance, they exhibit a pronounced resistance to chemo- and radiotherapy. More advanced [...] Read more.
Despite multimodal therapies, the treatment of glioblastoma remains challenging. In addition to the very complex mechanisms of cancer cells, including specialized phenotypes that enable them to proliferate, invade tissues, and evade immunosurveillance, they exhibit a pronounced resistance to chemo- and radiotherapy. More advanced tumors create a hypoxic environment that supports their proliferation and survival, while robust angiogenesis ensures a constant supply of nutrients. In GBM, these structures are very pronounced and contribute to the creation and maintenance of a highly immunosuppressive microenvironment that promotes tumor growth and immune escape. In addition, the high accumulation of immunosuppressive tumor-infiltrating leukocytes and other cells, the pronounced expression of immune checkpoint molecules, and the low mutational burden, i.e., the low number of neoantigens, are hallmarks of GBM and contribute to the challenge of therapeutic approaches. Here, we review a number of mechanisms that GBM exploits to support tumor growth and potential treatments. These include new chemotherapeutics, tumor treating fields, and small molecules, including compounds targeting angiogenesis or blockers of tyrosine kinases that inhibit tumor cell proliferation and survival. In addition, we focus on immunotherapies such as immune checkpoint blockade or cell therapies, in particular vaccination with dendritic cells and CAR-T cells, which can either kill GBM cells directly or bypass immunosuppression by modulating the tumor microenvironment or boosting the patient’s own immune response. Full article
(This article belongs to the Special Issue The Tumor Microenvironment: Interplay Between Immune Cells)
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20 pages, 2469 KiB  
Review
Neutrophil Engulfment in Cancer: Friend or Foe?
by Tong Lu and Wei Li
Cancers 2025, 17(3), 384; https://doi.org/10.3390/cancers17030384 - 24 Jan 2025
Cited by 1 | Viewed by 947
Abstract
Neutrophils, the most abundant circulating white blood cells, are essential for the initial immune response to infection and injury. Emerging research reveals a dualistic function of neutrophils in cancer, where they can promote or inhibit tumor progression. This dichotomy is influenced by the [...] Read more.
Neutrophils, the most abundant circulating white blood cells, are essential for the initial immune response to infection and injury. Emerging research reveals a dualistic function of neutrophils in cancer, where they can promote or inhibit tumor progression. This dichotomy is influenced by the tumor microenvironment, with neutrophils capable of remodeling the extracellular matrix, promoting angiogenesis, or alternatively inducing cancer cell death and enhancing immune responses. An intriguing yet poorly understood aspect of neutrophil–cancer interactions is the phenomenon of neutrophil engulfment by cancer cells, which has been observed across various cancers. This process, potentially mediated by LC3-associated phagocytosis (LAP), raises questions about whether it serves as a mechanism for immune evasion or contributes to tumor cell death through pathways like ferroptosis. This review examines current knowledge on neutrophil development, their roles in cancer, and the mechanisms of LAP in neutrophil engulfment by tumor cells. We discuss how manipulating LAP impacts cancer progression and may represent a therapeutic strategy. We also explore neutrophils’ potential as delivery vehicles for cancer therapeutic agents. Understanding the complex functions of tumor-associated neutrophils (TANs) and the molecular mechanisms underlying LAP in cancer may open new avenues for effective therapeutic interventions and mitigate potential risks. Full article
(This article belongs to the Special Issue The Tumor Microenvironment: Interplay Between Immune Cells)
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