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Biomedicines
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Tumor Immune Microenvironment and Novel Strategies for Cancer Immunotherapy
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Tumor Immune Microenvironment and Novel Strategies for Cancer Immunotherapy

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 5940

Special Issue Editor

Dr. Sidra Islam

E-Mail Website
Guest Editor
Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
Interests: protein biophysics; protein protein interactions; antioxidants; heme proteins; gamma crystallins

Special Issue Information

Dear Colleagues,

The Special Issue “Tumor Immune Microenvironment and Novel Strategies for Cancer Immunotherapy” encompasses a multidisciplinary field at the intersection of oncology, immunology, and therapeutics. It involves the study of complex interactions between cancer cells and the immune system within the microenvironment of tumors, as well as the development and implementation of innovative approaches to harness the immune system for treating cancer. The scope of this Special Issue includes investigating the cellular and molecular components of the tumor microenvironment, including tumor-infiltrating immune cells (such as T cells, B cells, natural killer cells, and myeloid cells), stromal cells, cytokines, chemokines, and extracellular matrix components; identifying biomarkers and predictive signatures associated with the tumor immune microenvironment; novel strategies for cancer immunotherapy aiming to manipulate the tumor immune microenvironment to enhance anti-tumor immune responses and overcoming immune evasion mechanisms employed by cancer cells; recognizing the complexity of the tumor immune microenvironment; combinatorial approaches that integrate immunotherapy with conventional treatments (such as chemotherapy, radiation therapy, and targeted therapy) or other immunomodulatory agents; combination therapies which have the potential to synergistically enhance therapeutic efficacy and overcome resistance mechanisms; translating preclinical findings and novel immunotherapeutic strategies into clinical practice, which requires rigorous clinical trials, biomarker validation studies, and collaborative efforts between researchers, clinicians, regulatory agencies, and industry partners.

In summary, this Special Issue encompasses a broad spectrum of research aimed at elucidating the complex interplay between tumors and the immune system, as well as the development of innovative immunotherapeutic approaches to combat cancer.

Dr. Sidra Islam
Guest Editor

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 short 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. Biomedicines is an international peer-reviewed open access monthly 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 2600 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 microenvironment cancer immunotherapy
  • immune markers
  • tumor infilterating immune cells
  • tumors

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Published Papers (5 papers)

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Research

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18 pages, 5615 KiB  
Article
Integrative Analysis of Neutrophil-Associated Genes Reveals Prognostic Significance and Immune Microenvironment Modulation in Cervical Cancer
by Ting Hu, Haijing Wu, Xinghan Cheng, Haoyue Gao and Min Yang
Biomedicines 2025, 13(6), 1348; https://doi.org/10.3390/biomedicines13061348 - 30 May 2025
Viewed by 361
Abstract
Background: Tumour-associated neutrophils play an important role in tumour progression and immunomodulation. However, the prognostic significance and immunological implications of neutrophil-associated genes (NAGS) in cervical cancer remain poorly defined. Methods: We analyzed neutrophil infiltration and its correlation with gene expression in TCGA cervical [...] Read more.
Background: Tumour-associated neutrophils play an important role in tumour progression and immunomodulation. However, the prognostic significance and immunological implications of neutrophil-associated genes (NAGS) in cervical cancer remain poorly defined. Methods: We analyzed neutrophil infiltration and its correlation with gene expression in TCGA cervical cancer data using immune deconvolution. NAGS were identified via correlation and enrichment analysis. A prognostic model was constructed using Cox and LASSO regression and validated in the GSE30759 cohort. Kaplan–Meier analysis, ROC curves, and multivariate Cox regression were used to assess prognostic performance. The model’s association with the tumor immune microenvironment and immunotherapy response was further analyzed. The expression pattern of SEMA6B was explored using cell lines, clinical subgroups, and human protein profiles, and its immunological relevance was evaluated using multiple immune infiltration algorithms. Results: Twelve genes were identified as significantly correlated with neutrophil infiltration and enriched in immune-related pathways such as chemotaxis, neutrophil degranulation, and PI3K-AKT signaling. Further NAGS models were developed based on key genes. High-risk patients exhibited an immunosuppressive tumor microenvironment, elevated TIDE scores, and lower predicted responsiveness to immunotherapy. SEMA6B was significantly downregulated in the tumour group but may be reactivated during metastasis. High expression of SEMA6B was associated with poorer prognostic features and immune evasion. Conclusions: We developed a NAGS signature that may inform prognosis and immune microenvironment status in cervical cancer. These findings suggest the potential clinical utility of NAGs-based models in guiding immunotherapy strategies. Moreover, SEMA6B may serve as a promising immunological and prognostic biomarker, pending further mechanistic validation. Full article
(This article belongs to the Special Issue Tumor Immune Microenvironment and Novel Strategies for Cancer Immunotherapy)
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19 pages, 8217 KiB  
Article
FAM111B Overexpression and Immune Cell Infiltration: Implications for Ovarian Cancer Immunotherapy
by Wanying Li, Fang Wei, Ting Zhou, Lijuan Feng and Lihong Zhang
Biomedicines 2025, 13(6), 1295; https://doi.org/10.3390/biomedicines13061295 - 24 May 2025
Viewed by 427
Abstract
Background: Ovarian cancer (OC) is characterized by high incidence and mortality rates; however, due to its immunologically “cold” phenotype, the effectiveness of immunotherapy as a strategy for OC remains inadequate. Although the FAM111B gene promotes the progression of various solid tumors, its [...] Read more.
Background: Ovarian cancer (OC) is characterized by high incidence and mortality rates; however, due to its immunologically “cold” phenotype, the effectiveness of immunotherapy as a strategy for OC remains inadequate. Although the FAM111B gene promotes the progression of various solid tumors, its specific function within the tumor immune microenvironment (TIME) of OC remains unclear. Methods: This study used multiplex immunofluorescence techniques and bioinformatics analysis to examine the role of FAM111B within the TIME of OC. Through multiplex immunofluorescence, we assessed the protein expression levels of FAM111B alongside key immune cell markers, including FOXP3, CD4, CD8, CD68, CD163, CD66b, and CD11c. Furthermore, we employed bioinformatics methods using The Cancer Genome Atlas database to validate FAM111B function at the mRNA level in OC. Results: We observed a positive correlation between FAM111B expression and immune cell infiltration, including T cells, macrophages, and dendritic cells. FAM111B, M2 macrophages, and regulatory T cells were associated with poorer overall survival in OC patients. Additionally, specific T cell subsets and dendritic cells were correlated positively with programmed death-ligand 1 expression, while FAM111B levels were linked to multiple immune checkpoint molecules. Conclusions: This study reveals a positive correlation between FAM111B overexpression and the infiltration levels of immune cells in OC. In OC patients characterized by elevated FAM111B expression, the potential augmentation of immune cell infiltration within the TIME may consequently enhance the efficacy of immunotherapy. Full article
(This article belongs to the Special Issue Tumor Immune Microenvironment and Novel Strategies for Cancer Immunotherapy)
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28 pages, 19771 KiB  
Article
Pan-Cancer Characterization Identifies SLC19A1 as an Unfavorable Prognostic Marker and Associates It with Tumor Infiltration Features
by Yimin Pan, Zhichen Liu and Changwu Wu
Biomedicines 2025, 13(3), 571; https://doi.org/10.3390/biomedicines13030571 - 25 Feb 2025
Viewed by 880
Abstract
Background: Recent studies have identified solute carrier family 19 member 1 (SLC19A1) as a second messenger transporter that regulates massive immune-related signaling cascades, but current studies provide limited information. This study aims to evaluate its role and the potential mechanisms across various cancers. [...] Read more.
Background: Recent studies have identified solute carrier family 19 member 1 (SLC19A1) as a second messenger transporter that regulates massive immune-related signaling cascades, but current studies provide limited information. This study aims to evaluate its role and the potential mechanisms across various cancers. Methods: We analyzed multi-omics data from a pan-cancer cohort to evaluate SLC19A1 expression and its association with multiple features, including prognosis, tumor stemness, genome instability, and immune infiltration. Immunofluorescence staining was performed to validate SLC19A1 expression in tumor tissues and its relationship M2 macrophages. In addition, we used web tools such as ROCplotter to evaluate the association between SLC19A1 and response to chemotherapy and immunotherapy. Results: SLC19A1 was found to be overexpressed in multiple cancer types compared to normal tissues, correlating with poor prognosis. High SLC19A1 levels were associated with increased genomic instability and immune suppression. In addition, SLC19A1 was negatively correlated with CD8+ T-cell infiltration and positively correlated with M2 macrophage infiltration. The association of SLC19A1 with M2 macrophages was confirmed in multiple immunofluorescence staining. Finally, SLC19A1 was associated with the response to chemotherapy and immunotherapy in a variety of tumors. Conclusions: Our findings position SLC19A1 as a novel unfavorable prognostic marker in cancer, closely linked to immune suppression and genomic instability. This study highlights the need for further exploration of SLC19A1 as a therapeutic target and its implications in cancer treatment strategies. Full article
(This article belongs to the Special Issue Tumor Immune Microenvironment and Novel Strategies for Cancer Immunotherapy)
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15 pages, 13837 KiB  
Article
Cordycepin Augments the Efficacy of Anti-PD1 against Colon Cancer
by Wen-Kuei Chang, Yen-Ting Chen, Chin-Ping Lin, Chia-Jung Wang, Hui-Ru Shieh, Chih-Wen Chi, Tung-Hu Tsai and Yu-Jen Chen
Biomedicines 2024, 12(7), 1568; https://doi.org/10.3390/biomedicines12071568 - 15 Jul 2024
Cited by 1 | Viewed by 1670
Abstract
Colon cancer has a poor clinical response to anti-PD1 therapy. This study aimed to evaluate the effect of cordycepin on the efficacy of anti-PD1 treatment in colon cancer. The viability of CT26 mouse colon carcinoma cells, cell-cycle progression, morphology, and the expression of [...] Read more.
Colon cancer has a poor clinical response to anti-PD1 therapy. This study aimed to evaluate the effect of cordycepin on the efficacy of anti-PD1 treatment in colon cancer. The viability of CT26 mouse colon carcinoma cells, cell-cycle progression, morphology, and the expression of mRNA and protein were assessed. A syngeneic animal model was established by implanting CT26 cells into BALB/c mice for in vivo experiments. Multi-parameter flow cytometry was used to analyze the splenic cell lineages and tumor microenvironment (TME). The in vitro data revealed that cordycepin, but not adenosine, inhibited CT26 cell viability. The protein, but not mRNA, expression levels of A2AR and A2BR were suppressed by cordycepin but not by adenosine in CT26 cells. The combination of cordycepin, but not adenosine, with anti-PD1 exhibited a greater tumor-inhibitory effect than anti-PD1 alone as well as inhibited the expression of A2AR and A2BR in splenic macrophages. In the TME, the combination of cordycepin and anti-PD1 increased the number of CD3+ T cells and neutrophils and decreased the number of natural killer (NK) cells. Overall, cordycepin augmented the antitumor effects of anti-PD1 against mouse colon carcinoma cells and inhibited the expression of the adenosine receptors A2AR and A2BR in splenic macrophages and intratumoral NK cells. Full article
(This article belongs to the Special Issue Tumor Immune Microenvironment and Novel Strategies for Cancer Immunotherapy)
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Review

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23 pages, 1061 KiB  
Review
Coley’s Toxin to First Approved Therapeutic Vaccine—A Brief Historical Account in the Progression of Immunobiology-Based Cancer Treatment
by K. Devaraja, Manisha Singh, Krishna Sharan and Sadhna Aggarwal
Biomedicines 2024, 12(12), 2746; https://doi.org/10.3390/biomedicines12122746 - 30 Nov 2024
Cited by 2 | Viewed by 1941
Abstract
Cancer immunobiology is one of the hot topics of discussion amongst researchers today, and immunotherapeutic modalities are among the selected few emerging approaches to cancer treatment that have exhibited a promising outlook. However, immunotherapy is not a new kid on the block; it [...] Read more.
Cancer immunobiology is one of the hot topics of discussion amongst researchers today, and immunotherapeutic modalities are among the selected few emerging approaches to cancer treatment that have exhibited a promising outlook. However, immunotherapy is not a new kid on the block; it has been around for centuries. The origin of cancer immunotherapy in modern medicine can be traced back to the initial reports of spontaneous regression of malignant tumors in some patients following an acute febrile infection, at the turn of the twentieth century. This review briefly revisits the historical accounts of immunotherapy, highlighting some of the significant developments in the field of cancer immunobiology, that have been instrumental in bringing back the immunotherapeutic approaches to the forefront of cancer research. Some of the topics covered are: Coley’s toxin—the first immunotherapeutic; the genesis of the theory of immune surveillance; the discovery of T lymphocytes and dendritic cells and their roles; the role of tumor antigens; relevance of tumor microenvironment; the anti-tumor (therapeutic) ability of Bacillus Calmette– Guérin; Melacine—the first therapeutic vaccine engineered; theories of immunoediting and immunophenotyping of cancer; and Provenge—the first FDA-approved therapeutic vaccine. In this review, head and neck cancer has been taken as the reference tumor for narrating the progression of cancer immunobiology, particularly for highlighting the advent of immunotherapeutic agents. Full article
(This article belongs to the Special Issue Tumor Immune Microenvironment and Novel Strategies for Cancer Immunotherapy)
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