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Cancer Immunology: From Molecular Mechanisms to Therapeutic Target through Emerging...
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Cancer Immunology: From Molecular Mechanisms to Therapeutic Target through Emerging In Vitro Approaches

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 21565

Special Issue Editor

Dr. Silvia Scaglione

E-Mail Website
Guest Editor
1. React4life SRL, 16121 Genova, Italy
2. National Research Council of Italy, Institute of Electronics, Information Engineering and Telecommunications (IEIIT), 16149 Genova, Italy
Interests: 3D tumor models; organ on chip; cells migration; drug efficacy; 3R in vitro approaches; immunooncology

Special Issue Information

Dear Colleagues,

In recent years, cancer immunotherapy has emerged as a promising therapeutic strategy to improve the treatment and benefits of individual patients. However, mechanisms behind tumor immunogenicity, immune cell invasion, adaptive immune responses against cancer, and escape mechanisms are still not completely elucidated.

In this context, the availability of more reliable preclinical models capable of recapitulating the real complexity of the human tumor microenvironment while overcoming the limitations of traditional approaches becomes mandatory. In particular, it is important to find ways to evolve current in vitro/in vivo models to become more predictive of the human patient heterogeneity and response to testing therapies.

This Special Issue will focus on translational research aimed at discussing the main challenges and possible future trends of cancer immunotherapies, by deepening novel and emerging in vitro approaches, such as immune component 3D tumor models, organ-on-chip technologies, tumor organoids, and 3D bioprinting.

Dr. Silvia Scaglione
Guest Editor

Manuscript Submission Information

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Keywords

  • immune-oncology
  • 3D tumor models
  • immune-tumor crosstalk
  • immune cells infiltration
  • immune-modulating agents
  • immune-organ on chip
  • spheroids
  • cell therapies

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Published Papers (4 papers)

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Review

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38 pages, 4554 KiB  
Review
Oncolytic Viruses and Immunotherapy for the Treatment of Uveal Melanoma and Retinoblastoma: The Current Landscape and Novel Advances
by Merve Kulbay, Nicolas Tuli, Massimo Mazza, Armaan Jaffer, Sarinee Juntipwong, Emily Marcotte, Stuti Misty Tanya, Anne Xuan-Lan Nguyen, Miguel N. Burnier, Jr. and Hakan Demirci
Biomedicines 2025, 13(1), 108; https://doi.org/10.3390/biomedicines13010108 - 6 Jan 2025
Viewed by 2232
Abstract
Intraocular malignant tumors are rare; however, they can cause serious life-threatening complications. Uveal melanoma (UM) and retinoblastoma (RB) are the most common intraocular tumors in adults and children, respectively, and come with a great disease burden. For many years, several different treatment modalities [...] Read more.
Intraocular malignant tumors are rare; however, they can cause serious life-threatening complications. Uveal melanoma (UM) and retinoblastoma (RB) are the most common intraocular tumors in adults and children, respectively, and come with a great disease burden. For many years, several different treatment modalities for UM and RB have been proposed, with chemotherapy for RB cases and plaque radiation therapy for localized UM as first-line treatment options. Extraocular extension, recurrence, and metastasis constitute the major challenges of conventional treatments. To overcome these obstacles, immunotherapy, which encompasses different treatment options such as oncolytic viruses, antibody-mediated immune modulations, and targeted immunotherapy, has shown great potential as a novel therapeutic tool for cancer therapy. These anti-cancer treatment options provide numerous advantages such as selective cancer cell death and the promotion of an anti-tumor immune response, and they prove useful in preventing vision impairment due to macular and/or optic disc involvement. Numerous factors such as the vector choice, route of administration, dosing, and patient characteristics must be considered when engineering an oncolytic virus or other forms of immunotherapy vectors. This manuscript provides an in-depth review of the molecular design of oncolytic viruses (e.g., virus capsid proteins and encapsulation technologies, vectors for delivery, cell targeting) and immunotherapy. The most recent advances in preclinical- and clinical-phase studies are further summarized. The recent developments in virus-like drug conjugates (i.e., AU011), oncolytic viruses for metastatic UM, and targeted immunotherapies have shown great results in clinical trials for the future clinical application of these novel technologies in the treatment algorithm of certain intraocular tumors. Full article
(This article belongs to the Special Issue Cancer Immunology: From Molecular Mechanisms to Therapeutic Target through Emerging In Vitro Approaches)
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15 pages, 1340 KiB  
Review
Indoleamine 2,3-Dioxygenase (IDO) Activity: A Perspective Biomarker for Laboratory Determination in Tumor Immunotherapy
by Pengbo Yang and Junhua Zhang
Biomedicines 2023, 11(7), 1988; https://doi.org/10.3390/biomedicines11071988 - 13 Jul 2023
Cited by 11 | Viewed by 3737
Abstract
Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme enzyme involved in catalyzing the conversion of tryptophan (Trp) into kynurenine (Kyn) at the first rate-limiting step in the kynurenine pathway of L-tryptophan metabolism. It has been found to be involved in several biological functions such [...] Read more.
Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme enzyme involved in catalyzing the conversion of tryptophan (Trp) into kynurenine (Kyn) at the first rate-limiting step in the kynurenine pathway of L-tryptophan metabolism. It has been found to be involved in several biological functions such as aging, immune microorganism, neurodegenerative and infectious diseases, and cancer. IDO1 plays an important role in immune tolerance by depleting tryptophan in the tumor microenvironment and inhibiting the proliferation of effector T cells, which makes it an important emerging biomarker for cancer immunotherapy. Therefore, the research and development of IDO1 inhibitors are of great importance for tumor therapy. Of interest, IDO activity assays are of great value in the screening and evaluation of inhibitors. Herein, we mainly review the biological functions of IDO1, immune regulation, key signaling molecules in the response pathway, and the development of IDO1 inhibitors in clinical trials. Furthermore, this review provides a comprehensive overview and, in particular, a discussion of currently available IDO activity assays for use in the evaluation of IDO inhibitors in human blood. We believe that the IDO activity is a promising biomarker for the immune escape and laboratory evaluation of tumor immunotherapy. Full article
(This article belongs to the Special Issue Cancer Immunology: From Molecular Mechanisms to Therapeutic Target through Emerging In Vitro Approaches)
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13 pages, 3068 KiB  
Review
Updates on Lymphovascular Invasion in Breast Cancer
by Elisabetta Kuhn, Donatella Gambini, Luca Despini, Dario Asnaghi, Letterio Runza and Stefano Ferrero
Biomedicines 2023, 11(3), 968; https://doi.org/10.3390/biomedicines11030968 - 21 Mar 2023
Cited by 25 | Viewed by 13062
Abstract
Traditionally, lymphovascular invasion (LVI) has represented one of the foremost pathological features of malignancy and has been associated with a worse prognosis in different cancers, including breast carcinoma. According to the most updated reporting protocols, the assessment of LVI is required in the [...] Read more.
Traditionally, lymphovascular invasion (LVI) has represented one of the foremost pathological features of malignancy and has been associated with a worse prognosis in different cancers, including breast carcinoma. According to the most updated reporting protocols, the assessment of LVI is required in the pathology report of breast cancer surgical specimens. Importantly, strict histological criteria should be followed for LVI assessment, which nevertheless is encumbered by inconsistency in interpretation among pathologists, leading to significant interobserver variability and scarce reproducibility. Current guidelines for breast cancer indicate biological factors as the main determinants of oncological and radiation therapy, together with TNM staging and age. In clinical practice, the widespread use of genomic assays as a decision-making tool for hormone receptor-positive, HER2-negative breast cancer and the subsequent availability of a reliable prognostic predictor have likely scaled back interest in LVI’s predictive value. However, in selected cases, the presence of LVI impacts adjuvant therapy. This review summarizes current knowledge on LVI in breast cancer with regard to definition, histopathological assessment, its biological understanding, clinicopathological association, and therapeutic implications. Full article
(This article belongs to the Special Issue Cancer Immunology: From Molecular Mechanisms to Therapeutic Target through Emerging In Vitro Approaches)
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Other

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14 pages, 638 KiB  
Study Protocol
The Prognostic and Predictive Value of Human Gastrointestinal Microbiome and Exosomal mRNA Expression of PD-L1 and IFNγ for Immune Checkpoint Inhibitors Response in Metastatic Melanoma Patients: PROTOCOL TRIAL
by Ana Erman, Marija Ignjatović, Katja Leskovšek, Simona Miceska, Urša Lampreht Tratar, Maša Bošnjak, Veronika Kloboves Prevodnik, Maja Čemažar, Lidija Kandolf Sekulovič, Gorazd Avguštin, Janja Ocvirk and Tanja Mesti
Biomedicines 2023, 11(7), 2016; https://doi.org/10.3390/biomedicines11072016 - 18 Jul 2023
Cited by 2 | Viewed by 1904
Abstract
Background: Immunotherapy has been successful in treating advanced melanoma, but a large proportion of patients do not respond to the treatment with immune checkpoint inhibitors (ICIs). Preclinical and small cohort studies suggest gastrointestinal microbiome composition and exosomal mRNA expression of PD-L1 and IFNγ [...] Read more.
Background: Immunotherapy has been successful in treating advanced melanoma, but a large proportion of patients do not respond to the treatment with immune checkpoint inhibitors (ICIs). Preclinical and small cohort studies suggest gastrointestinal microbiome composition and exosomal mRNA expression of PD-L1 and IFNγ from the primary tumor, stool and body fluids as potential biomarkers for response. Methods: Patients treated with immune checkpoint inhibitors as a first line treatment for metastatic melanoma are recruted to this prospective study. Stool samples are submitted before the start of treatment, at the 12th (+/−2) week and 28th (+/−2) week, and at the occurrence of event (suspected disease progression/hyperprogression, immune-related adverse event (irAE), deterioration). Peripheral venous blood samples are taken additionally at the same time points for cytologic and molecular tests. Histological material from the tumor tissue is obtained before the start of immunotherapy treatment. Primary objectives are to determine whether the human gastrointestinal microbiome (bacterial and viral) and the exosomal mRNA expression of PD-L1 and IFNγ and its dynamics predicts the response to treatment with PD-1 and CTLA-4 inhibitors and its association with the occurrence of irAE. The response is evaluated radiologically with imaging methods in accordance with the irRECIST criteria. Conclusions: This is the first study to combine and investigate multiple potential predictive and prognostic biomarkers and their dynamics in first line ICI in metastatic melanoma patients. Full article
(This article belongs to the Special Issue Cancer Immunology: From Molecular Mechanisms to Therapeutic Target through Emerging In Vitro Approaches)
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