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Cells
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Harnessing the Immune System to Fight Pediatric Cancer
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Harnessing the Immune System to Fight Pediatric Cancer

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 13061

Special Issue Editor

Dr. John M. Perry

E-Mail Website
Guest Editor
Children’s Mercy Research Institute, Kansas City, MO, USA
Interests: stem cells; immunotherapy; cancer stem cells; therapy resistance; drug discovery; pediatric cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pediatric cancer presents unique treatment challenges but also opportunities. Current treatment strategies typically involve the use of highly toxic drugs, which can result in life-long side effects. Treatment failure and relapse lead to increasingly worse outcomes and side effects from increasingly toxic therapies. Although children are not simply smaller adults, and pediatric cancers are fundamentally different in their etiology, treatments have largely been adapted from adult research. Pediatric cancers typically lack the large number of mutations that often make immunotherapy effective. However, genomic medicine offers the opportunity to identify genetic and, perhaps more importantly, epigenetic changes that might be targeted by molecular and immune-based therapies. This Special Issue will review how the genomes and epigenomes of pediatric patients are unique and potentially targetable. Identifying rare genetic and epigenetic variants that contribute to pediatric cancer will help to identify new treatment options. In addition, further development of immunotherapy for pediatric patients can improve the treatment paradigm and long-term outcomes for this unique population.

Dr. John M. Perry
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. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • Immunotherapy
  • CAR T cells
  • Therapy-resistance
  • Targeted therapy
  • Pediatric cancer
  • Pediatric genomics

Published Papers (4 papers)

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Review

11 pages, 785 KiB  
Review
Ectopic Tumor VCAM-1 Expression in Cancer Metastasis and Therapy Resistance
by Kristen A. VanHeyst, Sung Hee Choi, Daniel T. Kingsley and Alex Y. Huang
Cells 2022, 11(23), 3922; https://doi.org/10.3390/cells11233922 - 04 Dec 2022
Cited by 8 | Viewed by 2765
Abstract
Vascular Cell Adhesion Molecule-1 (VCAM-1; CD106) is a membrane protein that contributes critical physiologic functional roles in cellular immune response, including leukocyte extravasation in inflamed and infected tissues. Expressed as a cell membrane protein, VCAM-1 can also be cleaved from the cell surface [...] Read more.
Vascular Cell Adhesion Molecule-1 (VCAM-1; CD106) is a membrane protein that contributes critical physiologic functional roles in cellular immune response, including leukocyte extravasation in inflamed and infected tissues. Expressed as a cell membrane protein, VCAM-1 can also be cleaved from the cell surface into a soluble form (sVCAM-1). The integrin α4β1 (VLA-4) was identified as the first major ligand for VCAM-1. Ongoing studies suggest that, in addition to mediating physiologic immune functions, VCAM-1/VLA-4 signaling plays an increasingly vital role in the metastatic progression of various tumors. Additionally, elevated concentrations of sVCAM-1 have been found in the peripheral blood of patients with cancer, suggesting the tumor microenvironment (TME) as the source of sVCAM-1. Furthermore, over-expression of VLA-4 was linked to tumor progression in various malignancies when VCAM-1 was also up-regulated. This review explores the functional role of VCAM-1 expression in cancer metastasis and therapy resistance, and the potential for the disruption of VCAM-1/VLA-4 signaling as a novel immunotherapeutic approach in cancer, including osteosarcoma, which disproportionately affects the pediatric, adolescent and young adult population, as an unmet medical need. Full article
(This article belongs to the Special Issue Harnessing the Immune System to Fight Pediatric Cancer)
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33 pages, 3273 KiB  
Review
Molecular Markers of Pediatric Solid Tumors—Diagnosis, Optimizing Treatments, and Determining Susceptibility: Current State and Future Directions
by Joanna Trubicka, Wiesława Grajkowska and Bożenna Dembowska-Bagińska
Cells 2022, 11(7), 1238; https://doi.org/10.3390/cells11071238 - 06 Apr 2022
Cited by 7 | Viewed by 2529
Abstract
Advances in molecular technologies, from genomics and transcriptomics to epigenetics, are providing unprecedented insight into the molecular landscape of pediatric tumors. Multi-omics approaches provide an opportunity to identify a wide spectrum of molecular alterations that account for the initiation of the neoplastic process [...] Read more.
Advances in molecular technologies, from genomics and transcriptomics to epigenetics, are providing unprecedented insight into the molecular landscape of pediatric tumors. Multi-omics approaches provide an opportunity to identify a wide spectrum of molecular alterations that account for the initiation of the neoplastic process in children, response to treatment and disease progression. The detection of molecular markers is crucial to assist clinicians in accurate tumor diagnosis, risk stratification, disease subtyping, prediction of treatment response, and surveillance, allowing also for personalized cancer management. This review summarizes the most recent developments in genomics research and their relevance to the field of pediatric oncology with the aim of generating an overview of the most important, from the clinical perspective, molecular markers for pediatric solid tumors. We present an overview of the molecular markers selected based on therapeutic protocols, guidelines from international committees and scientific societies, and published data. Full article
(This article belongs to the Special Issue Harnessing the Immune System to Fight Pediatric Cancer)
42 pages, 1395 KiB  
Review
Insights into Modern Therapeutic Approaches in Pediatric Acute Leukemias
by Kinga Panuciak, Mikołaj Margas, Karolina Makowska and Monika Lejman
Cells 2022, 11(1), 139; https://doi.org/10.3390/cells11010139 - 02 Jan 2022
Cited by 6 | Viewed by 3860
Abstract
Pediatric cancers predominantly constitute lymphomas and leukemias. Recently, our knowledge and awareness about genetic diversities, and their consequences in these diseases, have greatly expanded. Modern solutions are focused on mobilizing and impacting a patient’s immune system. Strategies to stimulate the immune system, to [...] Read more.
Pediatric cancers predominantly constitute lymphomas and leukemias. Recently, our knowledge and awareness about genetic diversities, and their consequences in these diseases, have greatly expanded. Modern solutions are focused on mobilizing and impacting a patient’s immune system. Strategies to stimulate the immune system, to prime an antitumor response, are of intense interest. Amid those types of therapies are chimeric antigen receptor T (CAR-T) cells, bispecific antibodies, and antibody–drug conjugates (ADC), which have already been approved in the treatment of acute lymphoblastic leukemia (ALL)/acute myeloid leukemia (AML). In addition, immune checkpoint inhibitors (ICIs), the pattern recognition receptors (PRRs), i.e., NOD-like receptors (NLRs), Toll-like receptors (TLRs), and several kinds of therapy antibodies are well on their way to showing significant benefits for patients with these diseases. This review summarizes the current knowledge of modern methods used in selected pediatric malignancies and presents therapies that may hold promise for the future. Full article
(This article belongs to the Special Issue Harnessing the Immune System to Fight Pediatric Cancer)
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19 pages, 372 KiB  
Review
Genetic and Epigenetic Targeting Therapy for Pediatric Acute Lymphoblastic Leukemia
by Huan Xu, Hui Yu, Runming Jin, Xiaoyan Wu and Hongbo Chen
Cells 2021, 10(12), 3349; https://doi.org/10.3390/cells10123349 - 29 Nov 2021
Cited by 9 | Viewed by 2979
Abstract
Acute lymphoblastic leukemia is the most common malignancy in children and is characterized by numerous genetic and epigenetic abnormalities. Epigenetic mechanisms, including DNA methylations and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. Emerging studies [...] Read more.
Acute lymphoblastic leukemia is the most common malignancy in children and is characterized by numerous genetic and epigenetic abnormalities. Epigenetic mechanisms, including DNA methylations and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. Emerging studies are increasing our understanding of the epigenetic role of leukemogenesis and have demonstrated the potential of DNA methylations and histone modifications as a biomarker for lineage and subtypes classification, predicting relapse, and disease progression in acute lymphoblastic leukemia. Epigenetic abnormalities are relatively reversible when treated with some small molecule-based agents compared to genetic alterations. In this review, we conclude the genetic and epigenetic characteristics in ALL and discuss the future role of DNA methylation and histone modifications in predicting relapse, finally focus on the individual and precision therapy targeting epigenetic alterations. Full article
(This article belongs to the Special Issue Harnessing the Immune System to Fight Pediatric Cancer)
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