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Cells
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How Can We Optimise Cancer Therapy? Tumour Microenvironment and Immune...
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How Can We Optimise Cancer Therapy? Tumour Microenvironment and Immune Evasion Strategies

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

Deadline for manuscript submissions: 31 October 2025 | Viewed by 2008

Special Issue Editors

Prof. Dr. Agnieszka Bojarska-Junak

E-Mail Website
Guest Editor
Department of Clinical Immunology, Medical University of Lublin, 20-093 Lublin, Poland
Interests: cancer immunology; macrophages; myeloid-derived suppressor cells; γδ T cells; flow cytometry
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Michal Zarobkiewicz

E-Mail Website
Guest Editor
Department of Clinical Immunology, Medical University of Lublin, 20-093 Lublin, Poland.
Interests: flow cytometry; tumour immunology; autoimmunity; γδ T cells

Special Issue Information

Dear Colleagues,

The immune system is capable of reacting with malignant cells. However, this response is typically unsuccessful in advanced cancer. Cancer cells have developed complex mechanisms to prevent the immune system from detecting and eliminating them. Tumour antigen expression changes, increases in immune checkpoint receptor levels, metabolic networks, hypoxia, and the production of immunosuppressive factors are some of the mechanisms involved. In addition, the various triggered pathways can reprogram immune cells towards a regulatory phenotype or drive them into anergy. Therefore, to design new and more efficient anticancer treatments, it is necessary to understand the factors of the tumour microenvironment (TME) that affect the efficacy of immunotherapy. Oncological research requires a thorough understanding of the crosstalk between the tumour and the immune system.

This Special Issue is designed to encourage the exchange of findings in immuno-oncology related to cancer immune evasion, immunosuppression, and the microenvironment. Papers dealing with strategies for optimising cancer immunotherapy are especially welcome. Innovative original papers and reviews are within the scope of this Special Issue.

Prof. Dr. Agnieszka Bojarska-Junak
Prof. Dr. Michal Zarobkiewicz
Guest Editors

Manuscript Submission Information

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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. Cells 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 2700 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

  • immunosurveillance
  • immune evasion in cancer
  • tumour microenvironment
  • immune suppression
  • immunotherapy
  • immune checkpoints
  • cancer immunity
  • drug intervention

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Published Papers (3 papers)

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Research

29 pages, 4661 KiB  
Article
The Activity of Human NK Cells Towards 3D Heterotypic Cellular Tumor Model of Breast Cancer
by Anastasia Leonteva, Maria Abdurakhmanova, Maria Bogachek, Tatyana Belovezhets, Anna Yurina, Olga Troitskaya, Sergey Kulemzin, Vladimir Richter, Elena Kuligina and Anna Nushtaeva
Cells 2025, 14(14), 1039; https://doi.org/10.3390/cells14141039 - 8 Jul 2025
Viewed by 215
Abstract
Due to the complexity of modeling tumor-host interactions within the tumor microenvironment in vitro, we developed a 3D heterotypic cellular breast cancer (BC) model. We generated spheroid models using MCF7, MDA-MB-231, and SK-BR-3 cell lines alongside cancer-associated (BrC4f) and normal (BN120f) fibroblasts in [...] Read more.
Due to the complexity of modeling tumor-host interactions within the tumor microenvironment in vitro, we developed a 3D heterotypic cellular breast cancer (BC) model. We generated spheroid models using MCF7, MDA-MB-231, and SK-BR-3 cell lines alongside cancer-associated (BrC4f) and normal (BN120f) fibroblasts in ultra-low attachment plates. Stromal spheroids (3Df) were formed using a liquid overlay technique (graphical abstract). The YT cell line and peripheral blood NK (PB-NK) cells were used as immune components in our 3D model. In this study, we showed that stromal cells promoted tumor cell aggregation into spheroids, regardless of the initial proliferation rates, with NK cells accumulating in fibroblast-rich regions. The presence of CAFs within the model induced alterations in the expression levels of MICA/B and PD-L1 by tumor cells within the 3D-2 model. The feasibility of utilizing a 3D cell BC model in combination with cytokines and PB-NKs was evaluated. We observed that IL-15 and IL-2 enhanced NK cell activity within spheroids, whereas TGFβ had varying effects on proliferation depending on the cell type. Stimulation with IL-2 and IL-15 or TGFβ1 altered PB-NK markers and stimulated their differentiation into ILC1-like cells in 3D models. These findings underscore the regulatory function of CAFs in shaping the response of the tumor microenvironment to immunotherapeutic interventions. Full article
(This article belongs to the Special Issue How Can We Optimise Cancer Therapy? Tumour Microenvironment and Immune Evasion Strategies)
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Graphical abstract

21 pages, 3697 KiB  
Article
Characterization of Disseminated Tumor Cells (DTCs) in Patients with Triple-Negative Breast Cancer (TNBC)
by Anne Eckardt, Ivonne Nel, Laura Weydandt, Elisa Brochwitz, Anne Kathrin Höhn, Karsten Winter and Bahriye Aktas
Cells 2025, 14(12), 857; https://doi.org/10.3390/cells14120857 - 6 Jun 2025
Viewed by 467
Abstract
Triple negative breast cancer (TNBC) is the most aggressive molecular subtype and it lacks targetable receptors. Patients have an increased risk of recurrence and poor prognosis. Little is known concerning the characteristics of disseminated tumor cells (DTCs) and their role in TNBC patients. [...] Read more.
Triple negative breast cancer (TNBC) is the most aggressive molecular subtype and it lacks targetable receptors. Patients have an increased risk of recurrence and poor prognosis. Little is known concerning the characteristics of disseminated tumor cells (DTCs) and their role in TNBC patients. We analyzed the bone marrow aspirates of 80 patients with primary (n = 67) or recurrent (n = 13) TNBC, using a multi-parameter immunofluorescence staining procedure, including Pan-CK as an epithelial marker, vimentin (vim) as a marker of epithelial–mesenchymal transition, Ki67 for cell proliferation, and HER2 as well as PD-L1 as therapy-related markers. The DTC positive rate was 56% (n= 45) among the cohort. We found 20 different DTC subpopulations. The most frequently detected profile was CK+Vim+Ki67+ (n = 75 cells). The occurrence of CK- DTCs (n = 69) was significantly correlated to PD-L1 (r = −0.305, p < 0.01) and HER2 positivity (r = −0.234, p < 0.001). DTC positive patients that received neoadjuvant chemotherapy (NACT) and did not reach pathologic complete response were more likely to have CK- DTCs. Our data indicate that the occurrence of DTC subpopulations positive for Vim, Ki67, and HER2 appear to be markers for bad prognosis and could be therapeutically relevant. Furthermore, our results raise the question of whether DTCs are dormant in TNBC patients and persistent towards chemotherapy. Full article
(This article belongs to the Special Issue How Can We Optimise Cancer Therapy? Tumour Microenvironment and Immune Evasion Strategies)
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22 pages, 1359 KiB  
Article
Identification of B Cell Subpopulations with Pro- and Anti-Tumorigenic Properties in an Immunocompetent Mouse Model of Head and Neck Squamous Cell Carcinoma
by Michael Sonntag, Sandra Stanojevic, Simon Laban, Patrick J. Schuler, Thomas K. Hoffmann and Cornelia Brunner
Cells 2025, 14(1), 20; https://doi.org/10.3390/cells14010020 - 29 Dec 2024
Viewed by 922
Abstract
Due to their high developmental diversity and different regulatory and functional roles, B cell subpopulations can promote or inhibit tumor growth. An orthotopic murine HNSCC model was applied to investigate the B cell composition and function in HNSCCs. Using flow cytometry approaches, cells [...] Read more.
Due to their high developmental diversity and different regulatory and functional roles, B cell subpopulations can promote or inhibit tumor growth. An orthotopic murine HNSCC model was applied to investigate the B cell composition and function in HNSCCs. Using flow cytometry approaches, cells from the spleen, lymph nodes and tumors were analyzed. Additionally, immunoglobulin (Ig) levels post-tumor induction were tracked via enzyme-linked immunosorbent assays (ELISA). Following tumor induction, GCs, as well as increasing numbers of GL7+CD95+ GC B cells in the spleen and tumor tissues, were detected. In parallel, we observed CD39+CD73+ B cells in tumors and spleens of tumor-bearing mice. Notably, CD39+CD73+ expression was primarily detected on MZ B cells and to a lesser extent on follicular (FO) and non-follicular, newly formed (NF) B cells, supposing an immunosuppressive function of MZ B cells in the TME. Parallel to increased MZ B cell numbers in secondary lymphoid organs (SLOs) as well as in the tumor tissue, IgM antibody (Ab) levels rose continuously. In contrast, IgG1, IgG2, and IgG3 levels increased at later time points. Understanding the complex interactions between B cell subsets and the TME could lead to new strategies for enhancing the treatment and prognosis of HNSCC patients. Full article
(This article belongs to the Special Issue How Can We Optimise Cancer Therapy? Tumour Microenvironment and Immune Evasion Strategies)
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