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Tumor Microenvironment: Crosstalk Between Epigenetics, Metabolism and Immunity
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Tumor Microenvironment: Crosstalk Between Epigenetics, Metabolism and Immunity

A special issue of Current Issues in Molecular Biology (ISSN 1467-3045). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: 31 January 2026 | Viewed by 1408

Special Issue Editor

Dr. Liang Chen

E-Mail Website
Guest Editor
School of Medicine, Chongqing University, Chongqing, China
Interests: exosomes; metastatic spinal tumors; spinal trauma; intervertebral disc disease; degenerative spinal diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Tumors are known to be highly heterogeneous, with a proclivity for aggressive metastasis and drug resistance. These characteristics are linked to the tumor microenvironment, wherein tumor cells undergo metabolic reprogramming and epigenetic modifications; immune cells also produce reprogramming modifications. Because of these modifications, the tumor microenvironment becomes immunosuppressive, rendering tumor cells more susceptible to immune escape and drug resistance. This Special Issue aims to explore the interplay between epigenetic modifications, metabolic reprogramming, and immune escape mechanisms in the tumor microenvironment. By targeting these processes, the mechanisms of tumor therapeutic resistance can be better understood, thus providing potential targets and solutions for novel therapies, such as clinical immunotherapy.

We thank Dr. Xinyue Wan from Chongqing University for his contributions to this Special Issue’s proposal, development and promotion.

Dr. Liang Chen
Guest Editor

Manuscript Submission Information

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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. Current Issues in Molecular Biology 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 2200 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
  • epigenetic modifications
  • metabolic reprogramming
  • immune escape
  • tumor metastasis
  • therapeutic resistance

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Published Papers (2 papers)

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Research

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19 pages, 3108 KB  
Article
Caprylic Acid Restores Branched-Chain Amino Acid Metabolism in a Mouse Cachexia Model
by Isao Kawahara, Rina Fujiwara-Tani, Takuya Mori, Shota Nukaga, Ryoichi Nishida, Yoshihiro Miyagawa, Kei Goto, Hitoshi Ohmori, Kiyomu Fujii, Yi Luo, Takamitsu Sasaki, Chie Nakashima, Ruiko Ogata and Hiroki Kuniyasu
Curr. Issues Mol. Biol. 2025, 47(5), 325; https://doi.org/10.3390/cimb47050325 - 1 May 2025
Viewed by 762
Abstract
Cancer-associated sarcopenia is closely linked to the prognosis of cancer patients, making its management a critical aspect of cancer treatment. Branched-chain amino acids (BCAAs) are known to promote skeletal muscle growth in healthy individuals; however, their efficacy in cancer patients remains controversial. In [...] Read more.
Cancer-associated sarcopenia is closely linked to the prognosis of cancer patients, making its management a critical aspect of cancer treatment. Branched-chain amino acids (BCAAs) are known to promote skeletal muscle growth in healthy individuals; however, their efficacy in cancer patients remains controversial. In this study, we investigated the effects of BCAAs on cancer-associated sarcopenia to identify the underlying mechanisms that may suppress their effectiveness. In both a mouse cachexia model and an in vitro cachexia model, BCAAs did not significantly reduce oxidative stress, improve oxidative phosphorylation, suppress cytokine production, or enhance muscle mass and maturation, as observed in non-cancer-bearing models. Furthermore, treatment with 5-fluorouracil exacerbated sarcopenia in the mouse cachexia model, independent of tumor weight reduction, and this deterioration was not ameliorated by a BCAA-supplemented diet. The ineffectiveness of BCAAs was attributed to impaired BCAA catabolism, characterized by the decreased expression of branched-chain α-ketoacid dehydrogenase (BCKD) and increased levels of its inactive phosphorylated form, which were driven by elevated expression of BCKD kinase. These metabolic alterations were induced by high-mobility group box-1 (HMGB1). Notably, caprylic acid reversed these impairments in BCAA metabolism, thereby restoring BCAA efficacy. Our findings suggest that enhancing BCAA metabolism may improve their therapeutic potential in the treatment of cancer-associated sarcopenia. Full article
(This article belongs to the Special Issue Tumor Microenvironment: Crosstalk Between Epigenetics, Metabolism and Immunity)
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Review

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18 pages, 435 KB  
Review
Molecular and Glycosylation Pathways in Osteosarcoma: Tumor Microenvironment and Emerging Strategies Toward Personalized Oncology
by Georgian Longin Iacobescu, Antonio-Daniel Corlatescu, Horia Petre Costin, Razvan Spiridonica, Mihnea-Ioan-Gabriel Popa and Catalin Cirstoiu
Curr. Issues Mol. Biol. 2025, 47(8), 629; https://doi.org/10.3390/cimb47080629 - 7 Aug 2025
Viewed by 447
Abstract
Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical [...] Read more.
Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical and chemotherapeutic approaches, the presence of metastatic or recurrent disease is still detrimental to the patient’s outcome. Major advances in understanding the molecular mechanisms of OS are needed to substantially improve outcomes for patients being treated for OS. This review integrates new data on the molecular biology, pathophysiology, and immune landscape of OS, as well as introducing salient areas of tumorigenesis underpinning these findings, such as chromothripsis; kataegis; cancer stem cell dynamics; and updated genetic, epigenetic, and glycosylation modifiers. In addition, we review promising biomarkers, diagnostic platforms, and treatments, including immunotherapy, targeted small molecule inhibitors, and nanomedicine. Using genomic techniques, we have defined OS for its significant genomic instability due to TP53 and RB1 mutations, chromosomal rearrangements, and aberrant glycosylation. The TME is also characterized as immunosuppressive and populated by tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, ultimately inhibiting immune checkpoint inhibitors. Emerging fields such as glycomics and epigenetics, as well as stem cell biology, have defined promising biomarkers and targets. Preclinical studies have identified that glycan-directed CAR therapies could be possible, as well as metabolic inhibitors and 3D tumor models, which presented some preclinical success and could allow for tumoral specificity and enhanced efficacy. OS is a biologically and clinically complex disease; however, advances in exploring the molecular and immunologic landscape of OS present new opportunities in biomarkers and the development of new treatment options with adjunctive care. Successful treatments in the future will require personalized, multi-targeted approaches to account for tumor heterogeneity and immune evasion. This will help us turn the corner in providing improved outcomes for patients with this resilient malignancy. Full article
(This article belongs to the Special Issue Tumor Microenvironment: Crosstalk Between Epigenetics, Metabolism and Immunity)
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