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Biomedicines
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The Development of Cancer Immunotherapy (2nd Edition)
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The Development of Cancer Immunotherapy (2nd Edition)

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

Deadline for manuscript submissions: 31 July 2026 | Viewed by 2726

Editor

Prof. Dr. Satoshi Wada

E-Mail Website
Guest Editor
Department of Clinical Diagnostic Oncology, Showa Medical University Clinical Research Institute for Clinical Pharmacology and Therapeutics, 6-11-11 Kita-Karasuyama, Setagaya-ku, Tokyo 157-8577, Japan
Interests: cancer immunotherapy; biomarker; CAR-T; Immune checkpoint inhibitor; pancreatic cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The clinical development of cancer immunotherapy has been progressing rapidly, and since the Nobel Prize in Physiology or Medicine in 2018 was awarded in this area, it has been attracting more attention than ever before and is expected to develop further in the future. Immune checkpoint inhibitors were developed as drugs with a completely different mechanism to conventional chemotherapy for cancer patients, and their therapeutic effects were characterized not only by tumor shrinkage, but also by the long-term survival of cancer patients, which had a strong impact on cancer treatment. On the other hand, as a result of numerous clinical trials, it was found that the efficacy of immune checkpoint inhibitors alone is only approximately 10–20%. Another cancer immunotherapy, genetically modified T-cell therapy, has shown high efficacy against hematological cancers, but its effectiveness against solid tumors is yet to be proven. The aim of this Special Issue is to further develop cancer immunotherapy.

Prof. Dr. Satoshi Wada
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 250 words) can be sent to the Editorial Office for assessment.

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. Biomedicines is an international peer-reviewed open access monthly 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 2600 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

  • cancer immunotherapy
  • immune checkpoint inhibitors
  • genetically modified T-cell therapy
  • hematological cancers
  • solid tumors

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Related Special Issue

Published Papers (3 papers)

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Research

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21 pages, 4658 KB  
Communication
Preliminary Effects of Benralizumab in an AML Cell Model with Promyelocytic Features Expressing IL-5R: An Exploratory Proof-of-Concept Study
by Giovanna Lucia Piazzetta, Silvia Di Agostino, Nadia Lobello, Annamaria Aloisio, Anna Di Vito, Jessica Bria, Andrea Filardo, Isabella Coscarella, Mariaimmacolata Preianò, Corrado Pelaia, Nicola Lombardo and Emanuela Chiarella
Biomedicines 2026, 14(3), 652; https://doi.org/10.3390/biomedicines14030652 - 13 Mar 2026
Viewed by 637
Abstract
Background/Objectives: Acute myeloid leukemia (AML) comprises a heterogeneous group of diseases, with some subtypes displaying promyelocytic features and altered differentiation programs. Aberrant cytokine receptor signaling has been implicated in leukemogenesis, and IL-5Rα has recently emerged as a potential marker in selected AML subsets, [...] Read more.
Background/Objectives: Acute myeloid leukemia (AML) comprises a heterogeneous group of diseases, with some subtypes displaying promyelocytic features and altered differentiation programs. Aberrant cytokine receptor signaling has been implicated in leukemogenesis, and IL-5Rα has recently emerged as a potential marker in selected AML subsets, including promyelocytic variants. Benralizumab is a monoclonal antibody directed against the alpha chain of the interleukin-5 receptor (CD125), which blocks IL-5Rα–mediated signaling. This proof-of-concept study aimed to explore the effects of the anti-IL-5Rα monoclonal antibody Benralizumab in an in vitro AML cell model with promyelocytic characteristics. Methods: Public transcriptomic datasets were analyzed to evaluate IL-5Rα expression in AML subtypes. HL-60 cells, an AML cell line expressing IL-5Rα, were treated with Benralizumab and analyzed for cell cycle distribution and modulation of key signaling and apoptotic pathways by flow cytometry and Western blotting. Results: IL-5Rα was highly expressed in AML, particularly in M2 and M3 subtypes. Benralizumab treatment reduced STAT3 expression, activated ERK and NF-κB signaling, induced p21 and p27 expression, altered cell cycle distribution, and induced caspase-8 cleavage, suggesting activation of extrinsic apoptotic signaling. Conclusions: These findings provide preliminary proof-of-concept evidence that IL-5Rα targeting by Benralizumab may directly affect cell survival and cell cycle regulation in AML cells with promyelocytic characteristics. When interpreted together with the in silico analyses performed on AML patient datasets, these results support the rationale for future validation in APL-oriented models carrying the PML::RARα fusion, the disease-defining oncogenic driver generated by the t(15;17) translocation that blocks myeloid differentiation. However, the in silico and in vitro datasets were not formally integrated at the patient level, and these functional results should be considered exploratory. Full article
(This article belongs to the Special Issue The Development of Cancer Immunotherapy (2nd Edition))
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18 pages, 6641 KB  
Article
Age-Stratified Transcriptomic Profiling Reveals Biologically Distinct Molecular Phenotypes Across Pediatric, Adolescent, and Adult Osteosarcoma
by Li Hu, Feiyang Qi, Huimin Liu, Yiping Cao, Qinghua Li, Haijie Liang, Xingyu Liu, Zhiye Du, Yang Wang and Jichuan Wang
Biomedicines 2026, 14(2), 363; https://doi.org/10.3390/biomedicines14020363 - 4 Feb 2026
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Abstract
Background/Objectives: Osteosarcoma exhibits bimodal age distribution with distinct clinical behaviors between pediatric and adult patients. Despite genomic evidence supporting age-related molecular heterogeneity, systematic transcriptomic characterization remains lacking. This study aimed to delineate age-associated transcriptional differences and develop a pediatric-specific prognostic signature. Methods [...] Read more.
Background/Objectives: Osteosarcoma exhibits bimodal age distribution with distinct clinical behaviors between pediatric and adult patients. Despite genomic evidence supporting age-related molecular heterogeneity, systematic transcriptomic characterization remains lacking. This study aimed to delineate age-associated transcriptional differences and develop a pediatric-specific prognostic signature. Methods: Bulk RNA sequencing was performed on tumor specimens from 70 osteosarcoma patients stratified into pediatric (≤14 years, n = 37), adolescent (15–18 years, n = 22), and adult (≥19 years, n = 11) groups. Differential expression, functional enrichment, and immune infiltration analyses were conducted. A pediatric-specific signature was validated in the TARGET-OS cohort (n = 87). Results: Pediatric osteosarcoma exhibited a hyperproliferative phenotype, enriched in E2F targets, G2M checkpoint, and DNA replication pathways. Adolescent tumors showed heightened immune–inflammatory signatures, while adult tumors activated osteogenic differentiation programs. Regarding the immune microenvironment, only adolescent tumors demonstrated active immune infiltration; pediatric and adult groups exhibited immunologically “cold” features. We identified a 10-gene pediatric-specific transcriptomic signature that declined with increasing age. High signature scores were significantly associated with inferior overall survival (hazard ratio [HR] = 5.6, 95% confidence interval [CI]: 1.2–26.2, p = 0.01) and progression-free survival (HR = 2.1, 95% CI: 1.1–4.2, p = 0.03). These findings showed concordant trends in the independent TARGET-OS cohort. Conclusions: Pediatric, adolescent, and adult osteosarcoma harbor distinct transcriptional profiles representing biologically different disease entities. The pediatric-specific 10-gene signature may serve as a clinically actionable biomarker for risk stratification and guide age-adapted therapeutic strategies. Full article
(This article belongs to the Special Issue The Development of Cancer Immunotherapy (2nd Edition))
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Review

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19 pages, 369 KB  
Review
Evaluating the Therapeutic Impact of Immune Checkpoint Inhibitors in the Management of Brain Metastases from Non-Small Cell Lung Cancer
by Keren Rouvinov, Rashad Naamneh, Alexander Yakobson, Arina Soklakova, Wenad Najjar, Mahmoud Abu Amna, Mohnnad Asla, Ashraf Abu Jama, Nashat Abu Yasin, Mhammad Abu Juda, Sofyan Abu Freih, Yotam Malek and Walid Shalata
Biomedicines 2026, 14(3), 566; https://doi.org/10.3390/biomedicines14030566 - 2 Mar 2026
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Abstract
Background: Non-small cell lung cancer (NSCLC) patients often develop brain metastases (BMs), with an incidence rate of 25–40%. These metastases are associated with a poor prognosis. Although immune checkpoint inhibitors (ICIs) have revolutionized NSCLC treatment, their effectiveness against BMs remains not well-established. This [...] Read more.
Background: Non-small cell lung cancer (NSCLC) patients often develop brain metastases (BMs), with an incidence rate of 25–40%. These metastases are associated with a poor prognosis. Although immune checkpoint inhibitors (ICIs) have revolutionized NSCLC treatment, their effectiveness against BMs remains not well-established. This is primarily because patients with active or symptomatic BMs have frequently been excluded from clinical trials. Methods: To address the lack of data, in this narrative review, we searched the available clinical guidelines and relevant studies. Databases, including PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science, were searched for clinical studies published up to June 2025. The article included studies of NSCLC patients with BMs who were treated with ICIs and had reported central nervous system (CNS)-specific outcomes. Results: This article found that ICIs show significant intracranial activity. This activity is particularly notable in select NSCLC patients with asymptomatic BMs and high Programmed Death-Ligand 1 (PD-L1) expression. Conclusions: More research is needed to fully understand the efficacy of ICIs in treating BMs. Future prospective studies must include patients with active and symptomatic BMs to validate these findings and provide a clearer picture of ICI efficacy in this patient population. Full article
(This article belongs to the Special Issue The Development of Cancer Immunotherapy (2nd Edition))
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