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Advanced Molecular Science in Immunotherapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 9202

Special Issue Editor


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Guest Editor
COMT—Centre for Molecular and Translational Oncology, University of Parma, 43124 Parma, Italy
Interests: extracellular matrix; proteoglycans; immunotherapy; metastasis; angiogenesis; cell-matrix interactions; cancer stem cells; cell migration/invasion; tumour microenvironment
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Special Issue Information

Dear Colleagues,

Treating diseases with the novel generation of antibody-based/derived compounds is gradually supplanting the traditional pharmacology relying upon synthetic drugs and is the fulcrum of “immunotherapy”. It was through the revolutionizing hybridoma technology introduced by Kohler and Milstein that the use of monoclonal antibodies entered the therapeutic arena, with still a predominance in the cancer field. Clinical exploitation of such agents culminated in 1997 with the approval of the monoclonal antibody rituximab for the treatment of B-cell lymphomas. The classical approach of leveraging on immunological reagents targeting cancer cell-associated antigens also prevails now days, as such agents may be designed/engineered to induced direct cell killing through an associated cytotoxic payload (ADC, Antibody Drug Conjugates), or possibly through the triggering of cell-and/or complement-mediated cytotoxic effects. Alternative, antibody-based drugs progressively pervading the clinics are engineered molecular compounds construed as bispecific antibodies, in their full-length version or in the form of monovalent and bivalent immunoglobulin fragments and antibodies linked to other therapeutic proteins. We may therefore start to distinguish between “active”, or direct, and “passive”, or indirect, immunotherapy, conceived for producing either activating or suppressive outcomes depending on the pathological condition to be treated. Notably, we should acknowledge the idea of using anti-idiotypic antibodies for cancer therapy as the incipient lead to exploit (re)activation of the endogenous, innate immune system to attack cancer cells – an approach now considered revolutionary (and eloquently priced through a Nobel Price to the founders) in the context of antibody treatment of tumours. A further development of immunotherapy is finally provided by the combining of antibodies against elective cancer cell targets and the use of autologous immune cells (primarily T cells, known as T-cell adoptive transfer/CAR T cell therapy). This Special Issue aims to collect original research and review articles focusing on molecular advances in immunotherapy.

Prof. Dr. Roberto Perris
Guest Editor

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Keywords

  • antibody-drug conjugates
  • CAR T cells
  • immunotherapy
  • antibody therapy
  • antibody-induced cytotoxicity
  • bispecific antibodies
  • theranostic agents

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Published Papers (4 papers)

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Research

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22 pages, 3347 KiB  
Article
GLIS1, Correlated with Immune Infiltrates, Is a Potential Prognostic Biomarker in Prostate Cancer
by Qiang Peng, Tingting Xie, Yuliang Wang, Vincy Wing-Sze Ho, Jeremy Yuen-Chun Teoh, Peter Ka-Fung Chiu and Chi-Fai Ng
Int. J. Mol. Sci. 2024, 25(1), 489; https://doi.org/10.3390/ijms25010489 - 29 Dec 2023
Cited by 2 | Viewed by 1354
Abstract
Prostate cancer (PCa) is a prevalent malignant disease and the primary reason for cancer-related mortality among men globally. GLIS1 (GLIS family zinc finger 1) is a key regulator in various pathologies. However, the expression pattern, clinical relevance, and immunomodulatory function of GLIS1 in [...] Read more.
Prostate cancer (PCa) is a prevalent malignant disease and the primary reason for cancer-related mortality among men globally. GLIS1 (GLIS family zinc finger 1) is a key regulator in various pathologies. However, the expression pattern, clinical relevance, and immunomodulatory function of GLIS1 in PCa remain unclear. In this study, GLIS1 was discovered to serve as a key gene in PCa by integrating mRNA and miRNA expression profiles from GEO database. We systematically explored the expression and prognostic values of GLIS1 in cancers using multiple databases. Additionally, we examined the functions of GLIS1 and the relationship between GLIS1 expression levels and immune infiltration in PCa. Results showed that GLIS1 was differentially expressed between normal and tumor tissues in various cancer types and was significantly low-expressed in PCa. Low GLIS1 expression was associated with poor PCa prognosis. GLIS1 was also involved in the activation, proliferation, differentiation, and migration of immune cells, and its expression showed a positive correlation with the infiltration of various immune cells. Moreover, GLIS1 expression was positively associated with various chemokines/chemokine receptors, indicating the involvement in regulating immune cell migration. In summary, GLIS1 is a potential prognostic biomarker and a therapeutic target to modulate anti-tumor immune response in PCa. Full article
(This article belongs to the Special Issue Advanced Molecular Science in Immunotherapy)
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10 pages, 2285 KiB  
Communication
Memory Precursors and Short-Lived Effector T cell Subsets Have Different Sensitivities to TGFβ
by Jeremy A. O’Sullivan, Frederick J. Kohlhapp, Andrew Zloza, Lourdes Plaza-Rojas, Brianna Burke, Nickolai O. Dulin and José A. Guevara-Patiño
Int. J. Mol. Sci. 2023, 24(4), 3930; https://doi.org/10.3390/ijms24043930 - 15 Feb 2023
Cited by 1 | Viewed by 2566
Abstract
After exposure to an antigen, CD8 T cells reach a decision point about their fate: to become either short-lived effector cells (SLECs) or memory progenitor effector cells (MPECs). SLECs are specialized in providing an immediate effector function but have a shorter lifespan and [...] Read more.
After exposure to an antigen, CD8 T cells reach a decision point about their fate: to become either short-lived effector cells (SLECs) or memory progenitor effector cells (MPECs). SLECs are specialized in providing an immediate effector function but have a shorter lifespan and lower proliferative capacity compared to MPECs. Upon encountering the cognate antigen during an infection, CD8 T cells rapidly expand and then contract to a level that is maintained for the memory phase after the peak of the response. Studies have shown that the contraction phase is mediated by TGFβ and selectively targets SLECs, while sparing MPECs. The aim of this study is to investigate how the CD8 T cell precursor stage determines TGFβ sensitivity. Our results demonstrate that MPECs and SLECs have differential responses to TGFβ, with SLECs being more sensitive to TGFβ than MPECs. This difference in sensitivity is associated with the levels of TGFβRI and RGS3, and the SLEC-related transcriptional activator T-bet binding to the TGFβRI promoter may provide a molecular basis for increased TGFβ sensitivity in SLECs. Full article
(This article belongs to the Special Issue Advanced Molecular Science in Immunotherapy)
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Review

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18 pages, 332 KiB  
Review
Advancements in Allergen Immunotherapy for the Treatment of Atopic Dermatitis
by Bei-Cyuan Guo, Kang-Hsi Wu, Chun-Yu Chen, Wen-Ya Lin, Yu-Jun Chang, Mao-Jen Lin and Han-Ping Wu
Int. J. Mol. Sci. 2024, 25(2), 1316; https://doi.org/10.3390/ijms25021316 - 21 Jan 2024
Cited by 3 | Viewed by 2625
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects individuals of all age groups, manifesting as a spectrum of symptoms varying from mild to severe. Allergen immunotherapy (AIT) involves the administration of allergen extracts and has emerged as a potential treatment [...] Read more.
Atopic dermatitis (AD) is a chronic inflammatory skin condition that affects individuals of all age groups, manifesting as a spectrum of symptoms varying from mild to severe. Allergen immunotherapy (AIT) involves the administration of allergen extracts and has emerged as a potential treatment strategy for modifying immune responses. Its pathogenesis involves epidermal barrier dysfunction, microbiome imbalance, immune dysregulation, and environmental factors. Existing treatment strategies encompass topical steroids to systemic agents, while AIT is under investigation as a potential immune-modifying alternative. Several studies have shown reductions in the severity scoring of atopic dermatitis (SCORAD) scores, daily rescue medication use, and visual analog scale (VAS) scores following AIT. Biomarker changes include increased IgG4 levels and decreased eosinophil counts. This review provides valuable insights for future research and clinical practice, exploring AIT as a viable option for the management of AD. Full article
(This article belongs to the Special Issue Advanced Molecular Science in Immunotherapy)
12 pages, 969 KiB  
Review
Involvement of Embryo-Derived and Monocyte-Derived Intestinal Macrophages in the Pathogenesis of Inflammatory Bowel Disease and Their Prospects as Therapeutic Targets
by Shujun Zuo, Liping Jiang, Luying Chen, Weikang Wang, Jintao Gu, Jiajie Kuai, Xuezhi Yang, Yang Ma, Chenchen Han and Wei Wei
Int. J. Mol. Sci. 2024, 25(2), 690; https://doi.org/10.3390/ijms25020690 - 5 Jan 2024
Cited by 2 | Viewed by 1848
Abstract
Inflammatory bowel disease (IBD) is a group of intestinal inflammatory diseases characterized by chronic, recurrent, remitting, or progressive inflammation, which causes the disturbance of the homeostasis between immune cells, such as macrophages, epithelial cells, and microorganisms. Intestinal macrophages (IMs) are the largest population [...] Read more.
Inflammatory bowel disease (IBD) is a group of intestinal inflammatory diseases characterized by chronic, recurrent, remitting, or progressive inflammation, which causes the disturbance of the homeostasis between immune cells, such as macrophages, epithelial cells, and microorganisms. Intestinal macrophages (IMs) are the largest population of macrophages in the body, and the abnormal function of IMs is an important cause of IBD. Most IMs come from the replenishment of blood monocytes, while a small part come from embryos and can self-renew. Stimulated by the intestinal inflammatory microenvironment, monocyte-derived IMs can interact with intestinal epithelial cells, intestinal fibroblasts, and intestinal flora, resulting in the increased differentiation of proinflammatory phenotypes and the decreased differentiation of anti-inflammatory phenotypes, releasing a large number of proinflammatory factors and aggravating intestinal inflammation. Based on this mechanism, inhibiting the secretion of IMs’ proinflammatory factors and enhancing the differentiation of anti-inflammatory phenotypes can help alleviate intestinal inflammation and promote tissue repair. At present, the clinical medication of IBD mainly includes 5-aminosalicylic acids (5-ASAs), glucocorticoid, immunosuppressants, and TNF-α inhibitors. The general principle of treatment is to control acute attacks, alleviate the condition, reduce recurrence, and prevent complications. Most classical IBD therapies affecting IMs function in a variety of ways, such as inhibiting the inflammatory signaling pathways and inducing IM2-type macrophage differentiation. This review explores the current understanding of the involvement of IMs in the pathogenesis of IBD and their prospects as therapeutic targets. Full article
(This article belongs to the Special Issue Advanced Molecular Science in Immunotherapy)
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