Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Biomarkers in Cancer Immunology

Editor
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (20 April 2026) | Viewed by 17086

Share This Special Issue

Editor

Dr. Wioletta Olejarz

E-Mail Website
Guest Editor

Department of Biochemistry and Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warsaw, Poland
Interests: biochemistry; exosomes; DNA damage
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Cilleagues,

Cancer immunotherapy is now recognized as one of the main pillars of treatment alongside surgery, radiation, and chemotherapy. Targeted therapy and immunotherapy in combination are considered the ideal strategy for treating metastatic cancer, as this combination can eliminate primary tumors and induce host immunity to control distant metastases. Cancer immunotherapy harnesses the power of the host immune system to fight against cancer. Several types of immunotherapy, including adoptive cell transfer (ACT) and immune checkpoint inhibitors (ICIs), have achieved durable clinical responses, but their efficacies vary, and only subsets of cancer patients can benefit from them. Immune infiltrates in the tumor microenvironment (TME) have been shown to play a key role in tumor development and will affect the clinical outcomes of cancer patients. Comprehensive profiling of tumor-infiltrating immune cells would shed light on the mechanisms of cancer-immune evasion, thus providing opportunities for the development of novel therapeutic strategies. Importantly, Chimeric antigen receptor T (CAR-T) cell therapy achieved extraordinary results in antitumor treatments, especially against hematological malignancies, where it leads to remarkable, long-term antineoplastic effects with higher target specificity. Biomarkers play an important role in toxicity, relapse assessment, and efficacy prediction, and can be implicated in clinical applications of cancer immunotherapy and in establishing safe and efficacious personalized medicine. Therefore, improving our understanding of the progress in cancer immunotherapy may facilitate the elucidation of immune cell modulation in tumor progression.

Dr. Wioletta Olejarz
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. 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

immunotherapy
adoptive cell transfer
CAR-T cells
immune checkpoint inhibitors
tumor microenvironment
extracellular vesicles
biomarkers
miRNA
DNA

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (7 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

24 pages, 8889 KB

Open AccessArticle

SRC as a Prognostic and Immunomodulatory Biomarker in Acute Myeloid Leukemia: A Multi-Omics Study

by Jirui Zhong, Xikun Liu, Xuekui Gu and Zenghui Liu

Int. J. Mol. Sci. 2026, 27(9), 3734; https://doi.org/10.3390/ijms27093734 - 22 Apr 2026

Viewed by 1007

Abstract

The bone marrow tumor microenvironment (TME) is critical for acute myeloid leukemia (AML) progression, immune evasion, and treatment resistance. SRC, a non-receptor tyrosine kinase involved in multiple oncogenic pathways, has not been systematically characterized in AML in relation to prognosis and immune regulation. We integrated bulk transcriptomic and single-cell RNA-sequencing datasets from TCGA, BeatAML, and GEO. Immune-related targets were identified using xCell-based immune scoring and weighted gene co-expression network analysis (WGCNA), followed by protein–protein interaction analysis and multi-algorithm machine-learning screening. We then evaluated SRC expression patterns, prognostic associations, immune microenvironment features, predicted drug sensitivity, single-cell differentiation dynamics, intercellular communication, and in silico virtual knockout perturbation (scTenifoldKnk). SRC emerged as the most robust hub gene after integration of WGCNA, PPI analysis, machine-learning feature selection, and survival screening. SRC was significantly upregulated in AML compared with normal controls and was independently associated with poor overall survival (HR = 1.231, p = 0.037). High SRC expression was linked to adverse ELN/FAB features, increased immune checkpoint expression, enrichment of inflammatory and immunoregulatory pathways, and a higher proportion of primitive leukemia-associated cell states. Single-cell analyses further suggested that SRC was enriched in CD34⁺ progenitor compartments, associated with altered cell–cell communication, and accompanied by distinct mutation and pathway profiles. Drug-response prediction and in silico network perturbation analysis further supported the potential biological and translational relevance of SRC-centered programs. SRC is a prognostically relevant and immune-associated hub linked to AML microenvironment remodeling, and may serve as a candidate biomarker and potential therapeutic target that warrants further experimental validation. Full article

(This article belongs to the Special Issue Biomarkers in Cancer Immunology)

► Show Figures

Figure 1

33 pages, 14492 KB

Open AccessArticle

by Guoming Zhao, Xiaoqing Wang, Pengyu Yang, Peng Feng, Junqiang Dai, Liang Niu, Guoqiang Yuan and Yawen Pan

Int. J. Mol. Sci. 2026, 27(6), 2570; https://doi.org/10.3390/ijms27062570 - 11 Mar 2026

Viewed by 688

Abstract

Gliomas exhibit considerable molecular heterogeneity and immunological complexity, emphasizing the need for effective biomarkers and therapeutic targets. In this study, the Chinese Glioma Genome Atlas (CGGA-325/693) and The Cancer Genome Atlas (TCGA-LGG/GBM) cohorts were used to explore the pathological role of PHD finger protein 23 (PHF23) in gliomas. Machine learning algorithms were performed to construct a PHF23-related prognosis signature (PHF23-RPS). Our analysis revealed significant upregulation of PHF23 in high-grade gliomas, while the PHF23-RPS exhibited strong predictive performance (AUC = 0.853). Two molecular subtypes were identified; Cluster 2 was characterized as “inflamed yet immunosuppressive”. This subtype displayed a tumor mutational burden (TMB) paradox, where elevated TMB failed to translate into survival benefits due to extensive M2 macrophage infiltration and checkpoint-mediated immune exhaustion. Pharmacogenomic screening and molecular dynamics simulations identified Entospletinib as a potential candidate targeting this immunosuppressive barrier, showing a stable binding affinity (−7.7 kcal/mol). Functional assays, including in vitro experiments and in vivo experiments via a male BALB/c nude mouse orthotopic glioma model (n = 6/group), confirmed that PHF23 silencing inhibited glioma malignancy. Our results identify PHF23 as a critical oncogenic driver in glioma and support the PHF23-RPS for risk stratification. Entospletinib may offer a potential immunomodulatory option for high-risk gliomas. Full article

(This article belongs to the Special Issue Biomarkers in Cancer Immunology)

► Show Figures

Figure 1

24 pages, 872 KB

Open AccessArticle

The Roles of PD-L1, Ki-67, P53, and Cyclin D1 in PitNETs: Diagnostic and Prognostic Implications in a Series of 74 Patients

by Anna Krzentowska, Beata Biesaga, Ryszard Czepko, Anna Merklinger-Gruchała, Dariusz Adamek, Małgorzata Jasińska, Barbara Pluta, Wiktoria Michalska, Katarzyna Wróblewska, Filip Janczy and Filip Gołkowski

Int. J. Mol. Sci. 2025, 26(16), 7830; https://doi.org/10.3390/ijms26167830 - 13 Aug 2025

Cited by 4 | Viewed by 1957

Abstract

Pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas, are rare tumors that are usually benign. At present, the WHO PitNET classification based on transcription factors is in force. A problem is caused by invasive tumors and silent tumors which, despite a lack of obvious clinical symptoms, tend to behave aggressively. Factors influencing the clinical course of these tumors are currently being sought. The aim of our study was to assess the expression of programmed death-ligand 1 (PD-L1) and proliferation biomarkers (Ki-67, cyclin D1, and P53) in PitNETs depending on the transcription factor and adenoma subtype. The analysis was performed in seventy-four patients operated on in a single neurosurgical center for pituitary tumors. Immunohistochemistry was performed for transcription factors and biomarkers—PD-L1, Ki-67, P53, and cyclin D1—in tissue microarray format. Membranous expression of PD-L1 was scored as 0 (no expression) and ≥1%. Nuclear expression of Ki-67 was scored at <3% and ≥3%, and the expression of P53 and cyclin D1 was scored at <10% and ≥10%. The following tumors expressed PD-L1 at ≥1%: gonadotroph, 21 (28.4%); corticotroph, 5 (6.7%); gonadotroph/lactotroph, 2 (2.7%); null cell adenoma, 3 (4.0%); multiple synchronous PitNET, 2 (2.7%); immature PIT-1 tumor, 1 (1.3%); mature PIT-1 tumor, 1 (1.5%). Ki-67 ≥ 3% was found in the following PitNETs: gonadotroph, 3 (4.0%); corticotroph, 2 (2.7%); lactotroph, 1 (1.3%); multiple synchronous PitNET, 1 (1.3%); immature PIT-1 tumor, 1 (1.3%); and mature PIT-1 tumor, 1 (1.3%). Patients with Ki-67 ≥ 3% were statistically significantly younger (p = 0.03). All tumors (100%) with a combination of cyclin D1 ≥ 10% and P53 < 10% were invasive on the Hardy scale. Of the four factors, PD-L1 increased the odds of invasiveness the most (adjusted OR = 2.35; 95% CI: 0.56–9.90). PD-L1 expression was present in some types of PitNETs. PD-L1 expression may help in identifying null cell adenomas. High cyclin D1 with low P53 may indicate greater tumor invasiveness. Full article

(This article belongs to the Special Issue Biomarkers in Cancer Immunology)

► Show Figures

Figure 1

Review

Jump to: Research

22 pages, 1010 KB

Open AccessReview

Resistance to EGFR Inhibitors in NSCLC: Mechanistic Insights and Emerging Therapies

by Rita Khoury, Chris Raffoul, Colette Hanna, Khalil Saleh, Annoir Shayya, Meriana Nahouli and Hady Ghanem

Int. J. Mol. Sci. 2026, 27(12), 5197; https://doi.org/10.3390/ijms27125197 - 9 Jun 2026

Viewed by 280

Abstract

Non-small cell lung cancer (NSCLC) accounts for up to 85% of lung cancer cases, with activating EGFR mutations present in 10–15% of Western and up to 35% of Asian patients. EGFR tyrosine kinase inhibitors (TKIs) have transformed management, with first-line osimertinib demonstrating a median progression-free survival (PFS) of 18.9 months and overall survival (OS) of 38.6 months in the FLAURA trial. However, resistance inevitably develops, most commonly via T790M mutations (~50% of cases after first- and second-generation TKIs), and after osimertinib, through diverse mechanisms including C797S mutations, MET/HER2 amplification, and histologic transformation. Emerging strategies to overcome resistance include next-generation TKIs, combination targeted therapies, downstream pathway inhibitors, immunotherapy approaches, and antibody–drug conjugates. Understanding these mechanisms is critical for optimizing patient outcomes and guiding personalized therapeutic approaches. This review discusses current strategies to delay or overcome resistance and highlights emerging therapeutic avenues with the potential to reshape the management of EGFR-mutant NSCLC. Full article

(This article belongs to the Special Issue Biomarkers in Cancer Immunology)

► Show Figures

Figure 1

30 pages, 1343 KB

Open AccessReview

What Is—and What Is Not—Immunogenic Cell Death? Functional Definitions, Experimental Standards, and Common Pitfalls

by Diego Liviu Boaru, Oscar Fraile-Martinez, Patricia De Castro-Martinez, Miguel A. Ortega and Cielo Garcia-Montero

Int. J. Mol. Sci. 2026, 27(7), 3061; https://doi.org/10.3390/ijms27073061 - 27 Mar 2026

Cited by 1 | Viewed by 1005

Abstract

Immunogenic cell death (ICD) links tumor cell demise to the activation of anti-tumor immunity, but its adoption has also generated inconsistent definitions and frequent overinterpretation of surrogate biomarkers. Here, we synthesize mechanistic and methodological evidence showing that danger-associated molecular patterns (DAMPs), cytokine release, and endoplasmic reticulum stress report immunogenic potential rather than ICD itself. We propose that ICD should be defined by its functional immunological endpoint, namely efficient antigen presentation and antigen-specific adaptive immunity, ideally culminating in protective immunological memory. To operationalize this principle, we introduce a hierarchy of experimental validation ranging from correlative hallmarks (Level 0) to innate immune integration (Level 1), antigen-specific T-cell priming (Level 2), definitive vaccination-rechallenge protection with immune-dependence testing (Level 3), and translational relevance supported by convergent human data (Level 4). We also discuss common pitfalls, equating inflammation, necrosis-associated DAMP release, or therapeutic benefit with ICD, and outline minimal immune-context controls (e.g., MHC-I, CD8⁺ T cells, Batf3-dependent dendritic cells, and innate sensing pathways) required to support robust claims. Finally, we highlight why ICD remains strongly context-dependent, shaped by dendritic-cell competence, innate licensing, purinergic metabolism, and microenvironmental constraints. Evidence-graded standards should improve reproducibility, strengthen peer review, and accelerate clinically meaningful ICD-based strategies. Full article

(This article belongs to the Special Issue Biomarkers in Cancer Immunology)

► Show Figures

Figure 1

37 pages, 1448 KB

Open AccessReview

Immuno-Oncology at the Crossroads: Confronting Challenges in the Quest for Effective Cancer Therapies

by Claudiu Natanael Roznovan, Luminița Gabriela Măruțescu and Gratiela Gradisteanu Pircalabioru

Int. J. Mol. Sci. 2025, 26(13), 6177; https://doi.org/10.3390/ijms26136177 - 26 Jun 2025

Cited by 6 | Viewed by 3902

Abstract

Immuno-oncology has rapidly evolved into a cornerstone of modern cancer therapy, offering promising avenues for durable responses and personalized treatment strategies. This narrative review provides a thorough overview of the mechanisms underlying tumor–immune system interactions and the therapeutic innovations emerging from this knowledge. Central to this discussion is the tumor microenvironment (TME), a complex ecosystem of immune and stromal cells that supports tumor growth and shapes therapeutic outcomes. Key cellular and molecular factors within the TME are examined, along with diverse immune escape strategies. We further analyze the landscape of immunotherapeutic approaches, including immune checkpoint inhibitors, cancer vaccines, adoptive cell therapies such as CAR-T cells, and cytokine-based interventions. This review also addresses the increasing importance of predictive biomarkers in immuno-oncology, particularly in patient stratification, monitoring resistance, and managing immunotherapy-related toxicity. Finally, we explore the emerging role of the microbiome as a modulator of immunotherapy efficacy, shedding light on host–microbe–immune interactions that may influence clinical outcomes. By integrating current biological insights with therapeutic innovation, this review outlines the challenges and opportunities ahead in immuno-oncology and emphasizes the need for translational research and cross-disciplinary collaboration to optimize cancer immunotherapy in the era of precision medicine. Full article

(This article belongs to the Special Issue Biomarkers in Cancer Immunology)

► Show Figures

Figure 1

23 pages, 2364 KB

Open AccessReview

Advancements in Personalized CAR-T Therapy: Comprehensive Overview of Biomarkers and Therapeutic Targets in Hematological Malignancies

by Wioletta Olejarz, Karol Sadowski, Daniel Szulczyk and Grzegorz Basak

Int. J. Mol. Sci. 2024, 25(14), 7743; https://doi.org/10.3390/ijms25147743 - 15 Jul 2024

Cited by 19 | Viewed by 7313

Abstract

Chimeric antigen receptor T-cell (CAR-T) therapy is a novel anticancer therapy using autologous or allogeneic T-cells. To date, six CAR-T therapies for specific B-cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin lymphomas (NHL), and multiple myeloma (MM) have been approved by the Food and Drug Administration (FDA). Significant barriers to the effectiveness of CAR-T therapy include cytokine release syndrome (CRS), neurotoxicity in the case of Allogeneic Stem Cell Transplantation (Allo-SCT) graft-versus-host-disease (GVHD), antigen escape, modest antitumor activity, restricted trafficking, limited persistence, the immunosuppressive microenvironment, and senescence and exhaustion of CAR-Ts. Furthermore, cancer drug resistance remains a major problem in clinical practice. CAR-T therapy, in combination with checkpoint blockades and bispecific T-cell engagers (BiTEs) or other drugs, appears to be an appealing anticancer strategy. Many of these agents have shown impressive results, combining efficacy with tolerability. Biomarkers like extracellular vesicles (EVs), cell-free DNA (cfDNA), circulating tumor (ctDNA) and miRNAs may play an important role in toxicity, relapse assessment, and efficacy prediction, and can be implicated in clinical applications of CAR-T therapy and in establishing safe and efficacious personalized medicine. However, further research is required to fully comprehend the particular side effects of immunomodulation, to ascertain the best order and combination of this medication with conventional chemotherapy and targeted therapies, and to find reliable predictive biomarkers. Full article

(This article belongs to the Special Issue Biomarkers in Cancer Immunology)

► Show Figures

Journal Menu

Journal Browser

Biomarkers in Cancer Immunology

Share This Special Issue

Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (7 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI