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Biomedicines
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New Trends in Cancer Immunotherapy
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New Trends in Cancer Immunotherapy

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 May 2026) | Viewed by 3521

Editor

Dr. Markella Zannikou

E-Mail Website
Guest Editor
Feinberg School of Medicine, Northwestern University, 303 East Superior Ave., Chicago, IL 60611, USA
Interests: tumor microenvironment; cancer vaccines; tumor-infiltrating lymphocytes; combination therapy; BITEs; checkpoint inhibitors; CAR T cell therapy; NK cells; antigen presenting cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer is the second-leading cause of mortality globally. However, early diagnosis along with the development of novel immunotherapeutic approaches have significantly improved patient survival in recent decades. Cancer immunotherapy is a cutting-edge approach, which utilizes the immune system to identify and eradicate cancer cells. Nowadays, some of the most promising ways to treat cancer include therapeutic cancer vaccines, immune checkpoint inhibitors (like CTLA-4 and PD-1), bi-specific T-cell engagers (BiTEs), and adoptive cell therapies (ACTs). The stimulation of the T-cell-based immune response against tumor antigens by either endogenous or modified T cells is the common ground for all the scientific advances described above. Cancer immunotherapies are effective due to the interactions between the innate immune system, namely antigen-presenting and effector cells (T- and NK cells). Current methods that utilize these cells are under development.

Our goal in publishing this Special Issue "New Trends in Cancer Immunotherapy" is to further enhance the scientific interest in cancer immunotherapies, helping us to understand their mode of action, advantages, and limitations. This will promote the development of novel strategies for optimal clinical efficacy.

Dr. Markella Zannikou
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-anonymized 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

  • tumor microenvironment
  • cancer vaccines
  • tumor-infiltrating lymphocytes
  • combination therapy
  • BITEs
  • checkpoint inhibitors
  • CAR T cell therapy
  • NK cells
  • antigen presenting cells
  • tumor associated antigens

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Published Papers (3 papers)

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Research

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16 pages, 1199 KB  
Article
Comparative Prognostic Value of Systemic Inflammation-Based Biomarkers in Advanced Non-Small Cell Lung Cancer Treated with First-Line Immunotherapy
by Şahin Bedir, Gülin Alkan Şen, Hamza Abbasov, Murad Guliyev, Erdem Sünger, Burçin Çakan Demirel, Nilay Şengül, Abdilkerim Oyman, Yakup Bozkaya, Ahmet Bilici, Hande Turna, Mustafa Özgüroğlu and Gökmen Umut Erdem
Biomedicines 2026, 14(8), 1825; https://doi.org/10.3390/biomedicines14081825 - 13 Aug 2026
Viewed by 225
Abstract
Background: We assessed the prognostic value of the pan-immune–inflammation value (PIV), systemic immune–inflammation index (SII), lung immune prognostic index (LIPI), and c-reactive protein–albumin–lymphocyte (CALLY) index in advanced non-small cell lung cancer (NSCLC) treated with first-line immune checkpoint inhibitor (ICI)-based therapy. Methods: This multicenter [...] Read more.
Background: We assessed the prognostic value of the pan-immune–inflammation value (PIV), systemic immune–inflammation index (SII), lung immune prognostic index (LIPI), and c-reactive protein–albumin–lymphocyte (CALLY) index in advanced non-small cell lung cancer (NSCLC) treated with first-line immune checkpoint inhibitor (ICI)-based therapy. Methods: This multicenter retrospective study included 161 patients who received ICI monotherapy, chemoimmunotherapy, or dual ICI therapy. The objective response rate (ORR), clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS) were analyzed using Kaplan–Meier and Cox regression models. Results: A high CALLY index was associated with a significantly higher CBR (82.1% vs. 59.5%; p = 0.015), longer PFS (14.95 vs. 7.13 months; p = 0.002), and longer OS (25.79 vs. 13.24 months; p = 0.003). In the multivariable analyses, a high CALLY index remained independently associated with improved PFS (HR = 0.52, p = 0.006) and OS (HR = 0.53, p = 0.010), whereas a high SII was independently associated with poorer PFS (HR = 1.74, p = 0.021) and OS (HR = 1.90, p = 0.009). PIV and LIPI were not independently associated with survival outcomes. Conclusions: SII and the CALLY index emerged as independent prognostic biomarkers in advanced NSCLC receiving first-line immunotherapy-based treatment. The CALLY index showed the strongest and most consistent association with clinical benefit, PFS, and OS. Full article
(This article belongs to the Special Issue New Trends in Cancer Immunotherapy)
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31 pages, 4538 KB  
Article
Ex Vivo Traceability Platform for Phospholipoproteomic Formulations: Functional Evidence Without Clinical Exposure
by Ramón Gutiérrez-Sandoval, Francisco Gutiérrez-Castro, Natalia Muñoz-Godoy, Ider Rivadeneira, Andy Lagos, Ignacio Muñoz, Jordan Iturra, Francisco Krakowiak, Cristián Peña-Vargas, Matías Vidal and Andrés Toledo
Biomedicines 2025, 13(9), 2101; https://doi.org/10.3390/biomedicines13092101 - 28 Aug 2025
Cited by 2 | Viewed by 1466
Abstract
Background: Structurally active phospholipoproteomic formulations that lack pharmacodynamic targets or systemic absorption present unique challenges for validation. Designed for immune compatibility or structural modulation—rather than therapeutic effect—these platforms cannot be evaluated through conventional clinical or molecular frameworks. Methods: This study introduces a standardized, [...] Read more.
Background: Structurally active phospholipoproteomic formulations that lack pharmacodynamic targets or systemic absorption present unique challenges for validation. Designed for immune compatibility or structural modulation—rather than therapeutic effect—these platforms cannot be evaluated through conventional clinical or molecular frameworks. Methods: This study introduces a standardized, non-invasive ex vivo protocol using real-time kinetic imaging to document biological behavior under neutral conditions. Eight human tumor-derived adherent cell lines were selected for phenotypic stability and imaging compatibility. Phospholipoproteomic preparations were applied under harmonized conditions, and cellular responses were recorded continuously over 48 h. Results: Key parameters included signal continuity, morphological integrity, and inter-batch reproducibility. The system achieved high technical consistency without labeling, endpoint disruption, or destructive assays. Outputs included full kinetic curves and viability signals across multiple cell–fraction pairings. Conclusions: This method provides a regulatorily compatible foundation for functional documentation in non-pharmacodynamic programs where clinical trials are infeasible. It supports early-stage screening, batch comparability, and audit-ready records within SAP, CTD, or real-world evidence (RWE) ecosystems. By decoupling validation from systemic exposure, the protocol enables scalable, technically grounded decision-making for structurally defined immunobiological platforms. Full article
(This article belongs to the Special Issue New Trends in Cancer Immunotherapy)
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Review

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31 pages, 1406 KB  
Review
Challenges and Opportunities of γδ T Cell-Based Immunotherapy for Glioblastoma
by Chun-Chieh Chao, Hsieh-Tsung Ethan Shen, Bo-Xiang Benjamin Zhang, Ting-Hsuan Collette Chao, Ching-Dong William Wang and Chung-Che Wu
Biomedicines 2026, 14(8), 1770; https://doi.org/10.3390/biomedicines14081770 - 6 Aug 2026
Viewed by 608
Abstract
Glioblastoma remains the most lethal primary malignancy of the central nervous system, and the modest gains achieved with maximal surgery, radiotherapy and temozolomide have not been matched by the immune checkpoint inhibitors and antigen-specific vaccines that reshaped the treatment of many extracranial cancers. [...] Read more.
Glioblastoma remains the most lethal primary malignancy of the central nervous system, and the modest gains achieved with maximal surgery, radiotherapy and temozolomide have not been matched by the immune checkpoint inhibitors and antigen-specific vaccines that reshaped the treatment of many extracranial cancers. The recurrent disappointment of these approaches has been attributed less to a single molecular lesion than to a confluence of obstacles: profound intratumoural heterogeneity, a densely immunosuppressive and myeloid-rich microenvironment, sequestration and exhaustion of conventional T cells, and the practical difficulty of delivering effectors across the blood–brain barrier. Against this background, γδ T cells have attracted interest as an unconventional effector population that recognises transformed cells through stress-associated and metabolic cues rather than peptide–major histocompatibility complex (MHC) complexes, that kills in an MHC-unrestricted manner, and that can be expanded from healthy donors for allogeneic, off-the-shelf use with little expectation of graft-versus-host disease. This narrative review examines, with a deliberately critical lens, the biological rationale and the experimental evidence for γδ T cell-based immunotherapy of glioblastoma. We summarise the developmental biology and functional subsets of human γδ T cells, the natural killer group 2 member D (NKG2D)-, DNAX accessory molecule 1 (DNAM-1)- and T-cell-receptor-dependent mechanisms through which they engage glioblastoma cells and glioma stem-like cells, and the in vitro and animal-model studies that underpin the field, taking care not to overstate efficacy that has so far been demonstrated only in preclinical or early-phase settings. We then weigh the principal opportunities—locoregional and repeated dosing, combination with chemoradiotherapy, checkpoint blockade and antibody-based redirection—against barriers that include limited persistence, uncertain intratumoural trafficking, donor and manufacturing variability, and the unsettled requirements of potency testing and trial design. We give particular weight to what becomes of γδ T cells inside a hostile tumour—the exhaustion-like dysfunction that follows chronic stimulation, the oxygen and glucose dependence of their effector programme, the interleukin-17-polarising signals generated by activated microglia and by genotoxic therapy, and the confounding effect of corticosteroids—together with the engineering and pharmacological strategies proposed to counter them. The first peer-reviewed phase 1 report of intracranially delivered, drug-resistant γδ T cells has now appeared and documents tolerability in a small, single-arm cohort without establishing survival benefit. Throughout, γδ T cells are presented as a biologically plausible but still investigational strategy whose clinical value will be determined by adequately powered trials rather than by mechanistic appeal alone. Full article
(This article belongs to the Special Issue New Trends in Cancer Immunotherapy)
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