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Immunotherapy in Cancer: Molecular Basis and Novel Therapeutic Approaches
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Immunotherapy in Cancer: Molecular Basis and Novel Therapeutic Approaches

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: 20 February 2025 | Viewed by 6966

Special Issue Editor

Dr. Yonggu Lee

E-Mail Website
Guest Editor
College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 15588, Republic of Korea
Interests: research on the development of Chimeric Antigen Receptor (CAR) T cell treatment

Special Issue Information

Dear Colleagues,

Immunotherapy, from an immune checkpoint inhibitor to adoptive T-cell therapy, has emerged as a revolutionary paradigmatic shift in the field of cancer treatment. Unlike conventional treatments such as chemotherapy and radiation, which directly target tumor cells, immunotherapy provides novel approaches that redirect the immune system to combat malignant cells.

Understanding the molecular mechanisms of immunotherapy is essential for advancing our comprehension of how this revolutionary approach can reshape the landscape of cancer treatment. This knowledge could empower researchers, clinicians, and healthcare practitioners to make informed decisions, tailor treatments to individual patients, and design more effective therapeutic strategies.

This Special Issue of the International Journal of Molecular Sciences journal is designed to serve as a foundational guide for researchers, clinicians, and students seeking to comprehend the intricate molecular underpinnings of immunotherapeutic strategies in cancer treatment. By illuminating the synergistic dance between the immune system and cancer cells and by presenting the latest advancements in the field, this Special Issue fosters a deeper appreciation of the transformative potential of immunotherapy in reshaping the landscape of cancer therapy.

Dr. Yonggu Lee
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • cellular immunotherapy
  • adoptive immunotherapy
  • chimeric antigen receptor T-cell
  • epigenetic modulation
  • immunometabolism
  • microbiome
  • immune checkpoint inhibitor
  • cancer vaccine

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Published Papers (5 papers)

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Research

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27 pages, 4293 KiB  
Article
TGFB2 mRNA Levels Prognostically Interact with Interferon-Alpha Receptor Activation of IRF9 and IFI27, and an Immune Checkpoint LGALS9 to Impact Overall Survival in Pancreatic Ductal Adenocarcinoma
by Sanjive Qazi and Vuong Trieu
Int. J. Mol. Sci. 2024, 25(20), 11221; https://doi.org/10.3390/ijms252011221 - 18 Oct 2024
Viewed by 938
Abstract
The treatment of pancreatic ductal adenocarcinoma (PDAC) is an unmet challenge, with the median overall survival rate remaining less than a year, even with the use of FOLFIRINOX-based therapies. This study analyzed archived macrophage-associated mRNA expression using datasets deposited in the UCSC Xena [...] Read more.
The treatment of pancreatic ductal adenocarcinoma (PDAC) is an unmet challenge, with the median overall survival rate remaining less than a year, even with the use of FOLFIRINOX-based therapies. This study analyzed archived macrophage-associated mRNA expression using datasets deposited in the UCSC Xena web platform to compare normal pancreatic tissue and PDAC tumor samples. The TGFB2 gene exhibited low mRNA expression levels in normal tissue, with less than one TPM. In contrast, in tumor tissue, TGFB2 expression levels exhibited a 7.9-fold increase in mRNA expression relative to normal tissue (p < 0.0001). Additionally, components of the type-I interferon signaling pathway exhibited significant upregulation of mRNA levels in tumor tissue, including Interferon alpha/beta receptor 1 (IFNAR1; 3.4-fold increase, p < 0.0001), Interferon regulatory factor 9 (IRF9; 4.2-fold increase, p < 0.0001), Signal transducer and activator of transcription 1 (STAT1; 7.1-fold increase, p < 0.0001), and Interferon Alpha Inducible Protein 27 (IFI27; 66.3-fold increase, p < 0.0001). We also utilized TCGA datasets deposited in cBioportal and KMplotter to relate mRNA expression levels to overall survival outcomes. These increased levels of mRNA expression were found to be prognostically significant, whereby patients with high expression levels of either TGFB2, IRF9, or IFI27 showed median OS times ranging from 16 to 20 months (p < 0.01 compared to 72 months for patients with low levels of expression for both TGFB2 and either IRF9 or IFI27). Examination of the KMplotter database determined the prognostic impact of TGFB2 mRNA expression levels by comparing patients expressing high versus low levels of TGFB2 (50th percentile cut-off) in low macrophage TME. In TME with low macrophage levels, patients with high levels of TGFB2 mRNA exhibited significantly shorter OS outcomes than patients with low TGFB2 mRNA levels (Median OS of 15.3 versus 72.7 months, p < 0.0001). Furthermore, multivariate Cox regression models were applied to control for age at diagnosis. Nine genes exhibited significant increases in hazard ratios for TGFB2 mRNA expression, marker gene mRNA expression, and a significant interaction term between TGFB2 and marker gene expression (mRNA for markers: C1QA, CD74, HLA-DQB1, HLA-DRB1, HLA-F, IFI27, IRF9, LGALS9, MARCO). The results of our study suggest that a combination of pharmacological tools can be used in treating PDAC patients, targeting both TGFB2 and the components of the type-I interferon signaling pathway. The significant statistical interaction between TGFB2 and the nine marker genes suggests that TGFB2 is a negative prognostic indicator at low levels of the IFN-I activated genes and TAM marker expression, including the immune checkpoint LGALS9 (upregulated 16.5-fold in tumor tissue; p < 0.0001). Full article
(This article belongs to the Special Issue Immunotherapy in Cancer: Molecular Basis and Novel Therapeutic Approaches)
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15 pages, 3189 KiB  
Article
Lectin-like Transcript-1 (LLT1) Expression in Oral Squamous Cell Carcinomas: Prognostic Significance and Relationship with the Tumor Immune Microenvironment
by Juan C. de Vicente, Paloma Lequerica-Fernández, Juan P. Rodrigo, Tania Rodríguez-Santamarta, Verónica Blanco-Lorenzo, Llara Prieto-Fernández, Daniela Corte-Torres, Aitana Vallina, Francisco Domínguez-Iglesias, Saúl Álvarez-Teijeiro and Juana M. García-Pedrero
Int. J. Mol. Sci. 2024, 25(8), 4314; https://doi.org/10.3390/ijms25084314 - 13 Apr 2024
Viewed by 1357
Abstract
Lectin-like transcript-1 (LLT1) expression is detected in different cancer types and is involved in immune evasion. The present study investigates the clinical relevance of tumoral and stromal LLT1 expression in oral squamous cell carcinoma (OSCC), and relationships with the immune infiltrate into the [...] Read more.
Lectin-like transcript-1 (LLT1) expression is detected in different cancer types and is involved in immune evasion. The present study investigates the clinical relevance of tumoral and stromal LLT1 expression in oral squamous cell carcinoma (OSCC), and relationships with the immune infiltrate into the tumor immune microenvironment (TIME). Immunohistochemical analysis of LLT1 expression was performed in 124 OSCC specimens, together with PD-L1 expression and the infiltration of CD20+, CD4+, and CD8+ lymphocytes and CD68+ and CD163+-macrophages. Associations with clinicopathological variables, prognosis, and immune cell densities were further assessed. A total of 41 (33%) OSCC samples showed positive LLT1 staining in tumor cells and 55 (44%) positive LLT1 in tumor-infiltrating lymphocytes (TILs). Patients harboring tumor-intrinsic LLT1 expression exhibited poorer survival, suggesting an immunosuppressive role. Conversely, positive LLT1 expression in TILs was significantly associated with better disease-specific survival, and also an immune-active tumor microenvironment highly infiltrated by CD8+ T cells and M1/M2 macrophages. Furthermore, the combination of tumoral and stromal LLT1 was found to distinguish three prognostic categories (favorable, intermediate, and adverse; p = 0.029, Log-rank test). Together, these data demonstrate the prognostic relevance of tumoral and stromal LLT1 expression in OSCC, and its potential application to improve prognosis prediction and patient stratification. Full article
(This article belongs to the Special Issue Immunotherapy in Cancer: Molecular Basis and Novel Therapeutic Approaches)
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Review

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19 pages, 1669 KiB  
Review
Recent Advances in Artificial Intelligence to Improve Immunotherapy and the Use of Digital Twins to Identify Prognosis of Patients with Solid Tumors
by Laura D’Orsi, Biagio Capasso, Giuseppe Lamacchia, Paolo Pizzichini, Sergio Ferranti, Andrea Liverani, Costantino Fontana, Simona Panunzi, Andrea De Gaetano and Elena Lo Presti
Int. J. Mol. Sci. 2024, 25(21), 11588; https://doi.org/10.3390/ijms252111588 - 29 Oct 2024
Viewed by 827
Abstract
To date, the public health system has been impacted by the increasing costs of many diagnostic and therapeutic pathways due to limited resources. At the same time, we are constantly seeking to improve these paths through approaches aimed at personalized medicine. To achieve [...] Read more.
To date, the public health system has been impacted by the increasing costs of many diagnostic and therapeutic pathways due to limited resources. At the same time, we are constantly seeking to improve these paths through approaches aimed at personalized medicine. To achieve the required levels of diagnostic and therapeutic precision, it is necessary to integrate data from different sources and simulation platforms. Today, artificial intelligence (AI), machine learning (ML), and predictive computer models are more efficient at guiding decisions regarding better therapies and medical procedures. The evolution of these multiparametric and multimodal systems has led to the creation of digital twins (DTs). The goal of our review is to summarize AI applications in discovering new immunotherapies and developing predictive models for more precise immunotherapeutic decision-making. The findings from this literature review highlight that DTs, particularly predictive mathematical models, will be pivotal in advancing healthcare outcomes. Over time, DTs will indeed bring the benefits of diagnostic precision and personalized treatment to a broader spectrum of patients. Full article
(This article belongs to the Special Issue Immunotherapy in Cancer: Molecular Basis and Novel Therapeutic Approaches)
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14 pages, 873 KiB  
Review
Dual Roles of Host Zinc Finger Proteins in Viral RNA Regulation: Decay or Stabilization
by Hyokyoung Lee, Sung-Kyun Park and Junghyun Lim
Int. J. Mol. Sci. 2024, 25(20), 11138; https://doi.org/10.3390/ijms252011138 - 17 Oct 2024
Viewed by 749
Abstract
Host defense mechanisms against viral infections have been extensively studied over the past few decades and continue to be a crucial area of research in understanding human diseases caused by acute and chronic viral infections. Among various host mechanisms, recent findings have revealed [...] Read more.
Host defense mechanisms against viral infections have been extensively studied over the past few decades and continue to be a crucial area of research in understanding human diseases caused by acute and chronic viral infections. Among various host mechanisms, recent findings have revealed that several host RNA-binding proteins play pivotal roles in regulating viral RNA to suppress viral replication and eliminate infection. We have focused on identifying host proteins that function as regulators of viral RNA, specifically targeting viral components without adversely affecting host cells. Interestingly, these proteins exhibit dual roles in either restricting viral infections or promoting viral persistence by interacting with cofactors to either degrade viral genomes or stabilize them. In this review, we discuss RNA-binding zinc finger proteins as viral RNA regulators, classified into two major types: ZCCCH-type and ZCCHC-type. By highlighting the functional diversity of these zinc finger proteins, this review provides insights into their potential as therapeutic targets for the development of novel antiviral therapies. Full article
(This article belongs to the Special Issue Immunotherapy in Cancer: Molecular Basis and Novel Therapeutic Approaches)
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13 pages, 942 KiB  
Review
CD6 and Its Interacting Partners: Newcomers to the Block of Cancer Immunotherapies
by Lucía Aragón-Serrano, Laura Carrillo-Serradell, Violeta Planells-Romeo, Marcos Isamat, María Velasco-de Andrés and Francisco Lozano
Int. J. Mol. Sci. 2023, 24(24), 17510; https://doi.org/10.3390/ijms242417510 - 15 Dec 2023
Cited by 2 | Viewed by 2302
Abstract
Cancer management still requires more potent and safer treatments, of which immunomodulatory receptors on the lymphocyte surface have started to show promise in new cancer immunotherapies (e.g., CTLA-4 and PD-1). CD6 is a signal-transducing transmembrane receptor, mainly expressed by all T cells and [...] Read more.
Cancer management still requires more potent and safer treatments, of which immunomodulatory receptors on the lymphocyte surface have started to show promise in new cancer immunotherapies (e.g., CTLA-4 and PD-1). CD6 is a signal-transducing transmembrane receptor, mainly expressed by all T cells and some B and NK cell subsets, whose endogenous ligands (CD166/ALCAM, CD318/CDCP-1, Galectins 1 and 3) are overexpressed by malignant cells of different lineages. This places CD6 as a potential target for novel therapies against haematological and non-haematological malignancies. Recent experimental evidence for the role of CD6 in cancer immunotherapies is summarised in this review, dealing with diverse and innovative strategies from the classical use of monoclonal antibodies to soluble recombinant decoys or the adoptive transfer of immune cells engineered with chimeric antigen receptors. Full article
(This article belongs to the Special Issue Immunotherapy in Cancer: Molecular Basis and Novel Therapeutic Approaches)
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