The Immune Environment in Colorectal Adenoma: A Systematic ReviewSilinskaite, Valciukiene, Jakubauskas
et alBiomedicines (2025) 13 (3)
Abstract: Background/Objectives: Research on colorectal adenoma is significantly less comprehensive compared to studies on colorectal carcinoma. Although colorectal adenoma is a precursor of the majority of sporadic colorectal cancers, not all adenomas develop into carcinomas. The complex interaction of immune responses in the premalignant tumor microenvironment might be a factor for that. Methods: In this systematic review, we aim to provide a thorough analysis of the current research examining the immune infiltration patterns in sporadic colorectal adenoma tissues in the context of immune cell-based, cytokine-based, and other immunological factor-related changes along the conventional adenoma-carcinoma sequence. The articles included in the review extend up to December 2024 in PubMed and Web of Science databases. Results: Most included studies have shown significant differences in immune cell counts, densities, and cytokine expression levels associated with premalignant colorectal lesions (and/or colorectal cancer). No consensus on the immune-related tendencies concerning CD4+T cells and CD8+T cells was reached. Decreasing expression of mDCs and plasma and naïve B cells were detected along the ACS. The increased density of tissue eosinophils in the adenoma tissue dramatically diminishes after the transition to carcinoma. As the adenoma progresses, the increasing expression of IL-1α, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-21, IL-23, IL-33, and TGF-β and decreasing levels of IL-12A, IL-18, IFN-γ, and TNFα cytokines in the invasive carcinoma stage is being detected. The over-expression of COX-2, PD-1/PD-L1, CTLA-4, and ICOS/ICOSLG in the colorectal adenomatous and cancerous tissues was also observed. Conclusions: Further studies are needed for a better understanding of the whole picture of colorectal adenoma-associated immunity and its impact on precancerous lesion's potential to progress.
Advances in Liposomal Interleukin and Liposomal Interleukin Gene Therapy for Cancer: A Comprehensive Review of Preclinical StudiesKubbara, Bolad, Malibary
Pharmaceutics (2025) 17 (3)
Abstract: Preclinical studies on liposomal interleukin (IL) therapy demonstrate considerable promise in cancer treatment. This review explores the achievements, challenges, and future potential of liposomal IL encapsulation, focusing on preclinical studies.A structured search was conducted using the PubMed and Web of Science databases with the following search terms and Boolean operators: ("liposomal interleukin" OR "liposome-encapsulated interleukin") AND ("gene therapy" OR "gene delivery") AND ("cancer" OR "tumor" OR "oncology") AND ("pre-clinical studies" OR "animal models" OR "in vitro studies".Liposomal IL-2 formulations are notable for enhancing delivery and retention at tumor sites. Recombinant human interleukin (rhIL-2) adsorbed onto small liposomes (35-50 nm) substantially reduces metastases in murine models. Hepatic metastasis models demonstrate superior efficacy of liposomal IL-2 over free IL-2 by enhancing immune responses, particularly in the liver. Localized delivery strategies, including nebulized liposomal IL-2 in canine pulmonary metastases and intrathoracic administration in murine sarcoma models, reduce systemic toxicity while promoting immune activation and tumor regression. Liposomal IL gene therapy, delivering cytokine genes directly to tumor sites, represents a notable advancement. Combining IL-2 gene therapy with other cytokines, including IL-6 or double-stranded RNA adjuvants, synergistically enhances macrophage and T-cell activation. Liposomal IL-4, IL-6, and IL-21 therapies show potential across various tumor types. Pairing liposomal IL-2 with chemotherapy or immune agents improves remission and survival. Innovative strategies, including PEGylation and ligand-targeted systems, optimize delivery, release, and therapeutic outcomes.Utilizing immune-stimulatory ILs through advanced liposomal delivery and gene therapy establishes a strong foundation for advancing cancer immunotherapy.
Phenotypic and functional dysregulations of CD8 + T Cells in myasthenia gravisLiu, Zhang, Zhai
et alClin Exp Med (2025) 25 (1), 96
Abstract: Myasthenia Gravis (MG) is a heterogeneous autoimmune disorder characterized by fluctuating muscle weakness caused by autoantibodies targeting neuromuscular junction components. While the role of CD4 + T cells in MG is well established, the contribution of CD8 + T cells remains poorly understood. In this study, we analyze CD8 + T cells in 36 MG patients and 38 age- and gender-matched controls using flow cytometry to evaluate subset distribution, granzyme expression, and cytokine production. MG patients exhibit an altered CD4 + /CD8 + T cell ratio and significant changes in CD8 + T cell subsets, including increased central memory CD8 + T cell (Tcm) proportions and decreased effector memory CD8 + T cell (Tem) proportions. Granzyme B expression in Tcm cells is significantly elevated in MG patients, whereas no significant changes are observed in other subsets or GZMK expression. Cytokine analysis reveals increased IL-21, GM-CSF, and IL-17A production by CD8 + T cells in MG patients. These phenotypic and functional alterations of CD8 + T cells persist during the acute phase of the disease, regardless of immunotherapy usage, and vary between ocular and generalized MG. Subgroup and correlation analyses further identify age-dependent and age-independent dysregulations of CD8 + T cells, indicating complex and subtype-specific roles of CD8 + T cells in the immunopathological processes underlying MG. Our findings provide novel insights into the involvement of CD8 + T cells in MG pathogenesis, laying a foundation for future research and potential therapeutic strategies targeting CD8 + T cells.© 2025. The Author(s).
SHR0302 Improves Treg/Th17 Imbalance in Patients with Systemic Lupus ErythematosusMohammad, Jaafar, Maroof
Indian J Clin Biochem (2025) 40 (2), 274-283
Abstract: IL-6-mediated JAK1/STAT3 signaling pathway is involved in the development of Th17 cells, which play an essential role in the pathogenesis of various autoimmune diseases such as systemic lupus erythematosus (SLE). To evaluation of the regulatory and anti-inflammatory effects of the JAK1/STAT3 inhibition in SLE, we evaluated the effects of SHR0302 on regulatory T cell (Treg)/Th17 balance. Thirty-two patients with SLE and twenty-nine healthy subjects were enrolled in this study. The mRNA expression levels of anti- and pro-inflammatory cytokines, such as FOXP3, ROR-γt, IL-10, IL-17A, IL-21, and IRF-4, were determined using real-time PCR, and the cytokine levels of IL-6, IL-10, IL-17A, TNF-α, and IFN-γ were analyzed by ELISA. The frequency and in vitro development of CD4+ CD25+ Foxp3+ Treg and Th17 cells were evaluated by flow cytometry. SHR0302 could increase the mRNA expression and cytokine level of Treg-related molecules. Furthermore, numbers of Treg cells were increased, after treatment with SHR0302. In contrast, the mRNA expression level of Th17-related molecules, ROR-γt, IL-17A, and IL-21, were decreased. Reduction of inflammatory cytokine levels was a confirmation of the modulating effect of the SHR0302, including IL-6, IL-17, TNF-α, and IFN-γ. In addition, frequency of Th17 cells were reduced by SHR0302. Our study shows that SHR0302 regulating the JAK1/STAT3 pathway can be a new treatment option for SLE.© The Author(s), under exclusive licence to Association of Clinical Biochemists of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
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