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Tumor Microenvironment in Cancer: Basic Science, Artificial Intelligence, and Clinical...
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Tumor Microenvironment in Cancer: Basic Science, Artificial Intelligence, and Clinical Research

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

Deadline for manuscript submissions: closed (31 October 2025) | Viewed by 1471

Special Issue Editor

Dr. Rada Amin

E-Mail Website
Guest Editor
Department of Biochemistry, University of Nebraska-Lincoln, Lincoln, NE, USA
Interests: lymphoma; tumor microenvironment; immunotherapy; artificial intelligence
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The tumor microenvironment (TME) is a critical determinant of cancer progression, therapy resistance, and immune evasion, making it a key focus for innovative treatment strategies. Achieving a complete response remains challenging due to the persistence of drug-resistant clones supported by the TME and the multiple resistance mechanisms through which the TME counteracts therapy efficacy. The dynamic interactions between cancer stem cells, stromal components, immune infiltrates, and the extracellular matrix (ECM) create a highly adaptive and heterogeneous ecosystem that is difficult to predict and control. While immunotherapies, such as immune checkpoint inhibitors (ICIs), have shown promising results, the TME remains a major barrier to long-term efficacy due to its immunosuppressive nature and therapy-induced adaptations.

Therefore, innovative research is needed to unravel the complex molecular and cellular landscape of the TME and to identify novel targets to reduce relapse, overcome resistance, and prevent drug-resistant clones.

This Special Issue welcomes reviews and research articles spanning basic science to artificial intelligence approaches aimed at enhancing our understanding of the influence of TME on malignancies and improving therapeutic strategies.

Dr. Rada Amin
Guest Editor

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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

  • tumor microenvironment
  • cancer progression
  • malignancies
  • immunotherapy
  • therapy resistance
  • immune evasion

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Published Papers (2 papers)

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Research

15 pages, 1592 KB  
Article
Genetic Aberrations in Normal Tissues Adjacent to Biliary Tract Cancers
by Chae Hwa Kwon, Sung Hee Park, Hye Ji Lee, Jong Hyun Lee, Sung Yong Han, Yong Mok Park, Hyung Il Seo, Dong Uk Kim and Byeong Gwan Noh
Biomedicines 2025, 13(11), 2812; https://doi.org/10.3390/biomedicines13112812 - 18 Nov 2025
Viewed by 386
Abstract
Background: The role of normal tissues adjacent to tumors (NATs) in biliary tract cancer (BTC) remains unclear, despite their potential contributions to field cancerization. Methods: Targeted genomic profiling of tumor tissues, patient-matched NATs, and peripheral blood leukocytes from 13 patients with [...] Read more.
Background: The role of normal tissues adjacent to tumors (NATs) in biliary tract cancer (BTC) remains unclear, despite their potential contributions to field cancerization. Methods: Targeted genomic profiling of tumor tissues, patient-matched NATs, and peripheral blood leukocytes from 13 patients with BTCs was performed. Clinicopathological data, including inflammatory conditions and precursor lesions (biliary intraepithelial neoplasia [BilIN] and intraductal papillary neoplasm of the bile duct), were integrated with genomic findings. Results: Tumor tissues exhibited recurrent alterations in genes regulating DNA damage response, cell cycle control, and oncogenic signaling. Importantly, rather than being genetically silent, NATs harbor early somatic variants distinct from those in both tumor and germline DNA. These alterations were not directly associated with cancer-related pathways, but rather with extracellular matrix-receptor interactions, suggesting that NATs may represent an intermediate step in carcinogenesis. All patients with extrahepatic cholangiocarcinoma presented with BilIN in adjacent tissues, providing histological evidence of field cancerization linked to chronic inflammation. Conclusions: This systematic comparison of tumors, NATs, and germline DNAs in BTCs revealed that NATs contain biologically relevant somatic mutations. The concordance between the inflammatory background, precursor lesions, and genomic alterations supports a multistep carcinogenic model and highlights opportunities for early BTC detection and risk stratification. Full article
(This article belongs to the Special Issue Tumor Microenvironment in Cancer: Basic Science, Artificial Intelligence, and Clinical Research)
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17 pages, 3037 KB  
Article
Programmed-Cell-Death-Related Signature Reveals Immune Microenvironment Characteristics and Predicts Therapeutic Response in Diffuse Large B Cell Lymphoma
by Donghui Xing, Kaiping Luo, Xiang He, Xin Hu, Yixin Zhai, Yanan Jiang, Wenqi Wu and Zhigang Zhao
Biomedicines 2025, 13(10), 2320; https://doi.org/10.3390/biomedicines13102320 - 23 Sep 2025
Cited by 1 | Viewed by 736
Abstract
Background/Objectives: Diffuse large B cell lymphoma (DLBCL) is a highly heterogeneous and aggressive lymphoma with a high incidence rate. Although modern therapeutic approaches have significantly improved patient survival rates, treatment relapse and drug resistance remain major clinical challenges. Programmed cell death (PCD) [...] Read more.
Background/Objectives: Diffuse large B cell lymphoma (DLBCL) is a highly heterogeneous and aggressive lymphoma with a high incidence rate. Although modern therapeutic approaches have significantly improved patient survival rates, treatment relapse and drug resistance remain major clinical challenges. Programmed cell death (PCD) promotes tumorigenesis and regulates the tumor microenvironment (TME) and drug sensitivity. Exploring the application potential of PCD in DLBCL could pave the way for new treatment strategies for this malignancy. Methods: We systematically analyzed 13 types of PCD pathways and integrated transcriptomic and clinical data from 832 DLBCL patients (GSE10846, GSE11318, and GSE87371). A PCD-based prognostic signature, termed the Programmed Cell Death Score (PCDS), was constructed using 20 key PCD-related genes. Its clinical relevance was evaluated through survival analysis, drug response profiling, and tumor immune infiltration assessment using CIBERSORT, ESTIMATE, and ssGSEA algorithms. Results: The PCDS robustly stratified patients by survival and outperformed conventional clinical indicators such as age, stage, Eastern Cooperative Oncology Group (ECOG), and lactate dehydrogenase (LDH) in prognostic prediction. High-PCDS tumors were associated with immune suppression, characterized by reduced CD8+ T cell infiltration, elevated M2 macrophages, and increased programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) expression. Drug sensitivity analysis revealed that high-PCDS patients may benefit more from agents like sorafenib and fulvestrant, while low-PCDS patients responded better to NU7441. Functional validation using DLBCL cell lines and xenografts confirmed the oncogenic role of a representative gene (CTH) within the model. Conclusions: This study presents a novel prognostic scoring system derived from multiple PCD pathways that effectively stratifies DLBCL patients by risk and therapeutic responsiveness. Notably, the PCDS is closely associated with key immunological characteristics of the TME. These findings advance personalized treatment strategies and support clinically relevant decision-making in DLBCL. Full article
(This article belongs to the Special Issue Tumor Microenvironment in Cancer: Basic Science, Artificial Intelligence, and Clinical Research)
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