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The efficacy of cancer therapies is limited to a great extent by immunosuppressive mechanisms within the tumor microenvironment (TME). Numerous immune escape mechanisms have been identified. These include not only processes associated with tumor, immune or stromal cells, but also humoral, metabolic, genetic and epigenetic factors within the TME. The identification of immune escape mechanisms has enabled the development of small molecules, nanomedicines, immune checkpoint inhibitors, adoptive cell and epigenetic therapies that can reprogram the TME and shift the host immune response towards promoting an antitumor effect. These approaches have translated into series of breakthroughs in cancer therapies, some of which have already been implemented in clinical practice. In the present article the authors provide an overview of some of the most important mechanisms of immunosuppression within the TME and the implications for targeted therapies against different cancers.
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http://dx.doi.org/10.3389/fonc.2023.1200646 | DOI Listing |
Nano Lett
September 2025
Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha 410082, China.
Interleukin-12 (IL-12) is a robust proinflammatory cytokine that activates immune cells, such as T cells and natural killer cells, to induce antitumor immunity. However, the clinical application of recombinant IL-12 has been limited by systemic immune-related adverse events (irAEs) and rapid degradation. To address these challenges, we employed mRNA technology to encode a tumor-activated IL-12 "lock" fusion protein that offers both therapeutic efficacy and systemic safety.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
September 2025
Department of Gastroenterology, Jinhua Central Hospital, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, 321000, Zhejiang, China.
The fourth leading cause of cancer-related fatalities in the USA is pancreatic ductal adenocarcinoma (PDAC), a particularly deadly illness that is resistant to immunotherapy. One of the Main Obstacles in cancer research is developing better treatments for PDAC, which has the lowest 5-year survival rate of any malignancy. Anti-CTLA-4, anti-PD-L1, and anti-PD-1 immune checkpoint blockade medications also have poor results in these patients, which may indicate the presence of other immunosuppressive mechanisms in the pancreatic tumor microenvironment (TME).
View Article and Find Full Text PDFMed Oncol
September 2025
Department of Biotechnology, Institute of Engineering and Management, University of Engineering and Management, Kolkata, Kolkata, India.
Oligomeric proanthocyanidins (OPCs), condensed tannins found plentiful in grape seeds and berries, have higher bioavailability and therapeutic benefits due to their low degree of polymerization. Recent evidence places OPCs as effective modulators of cancer stem cell (CSC) plasticity and tumor growth. Mechanistically, OPCs orchestrate multi-pathway inhibition by destabilizing Wnt/β-catenin, Notch, PI3K/Akt/mTOR, JAK/STAT3, and Hedgehog pathways, triggering β-catenin degradation, silencing stemness regulators (OCT4, NANOG, SOX2), and stimulating tumor-suppressive microRNAs (miR-200, miR-34a).
View Article and Find Full Text PDFElife
September 2025
Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Immunogenic cell death (ICD) is a type of cell death sparking adaptive immune responses that can reshape the tumor microenvironment. Exploring key ICD-related genes in bladder cancer (BLCA) could enhance personalized treatment. The Cancer Genome Atlas (TCGA) BLCA patients were divided into two ICD subtypes: ICD-high and ICD-low.
View Article and Find Full Text PDFCancer Immunol Res
September 2025
Alligator Bioscience (Sweden), Lund, Sweden.
Despite recent progress within the field of immuno-oncology, immune suppression in the tumor microenvironment, defective antigen presentation, and low levels of tumor-specific T cells are key limitations of current cancer immunotherapies. CD40-targeting immunotherapies hold promises for addressing these limitations across solid tumors. Here, we describe ATOR-4066, a bispecific antibody that targets CD40 and CEACAM5 developed for immunotherapy of cancer using the Neo-X-Prime platform.
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