---
title: "Cellular Metabolism, Immunity, and Oncogenesis: Drug Discovery Opportunities"
id: "frontiers-in-immunology-5-editorial-cellular-metabolism-the-immune-system-and-oncogenesis-opportunities"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-5-editorial-cellular-metabolism-the-immune-system-and-oncogenesis-opportunities"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1997905"
published_at: "2026-09-23T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Cellular Metabolism, Immunity, and Oncogenesis: Drug Discovery Opportunities
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-5-editorial-cellular-metabolism-the-immune-system-and-oncogenesis-opportunities
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1997905)
- **Published At:** 2026-09-23T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The source article is an editorial exploring links among **cellular metabolism**, the **immune system**, and **oncogenesis**, with interest in implications for **drug discovery** and development. - The published page available in the source contains site navigation, journal sections, and journal information but does not include the editorial text or specific findings. - No study data, experiment descriptions, mechanistic details, therapeutic targets, or development recommendations were reported in the provided source content. - Because the source content is limited to journal and site metadata, substantive details such as proposed metabolic pathways, immune cell phenotypes, oncogenic mechanisms, candidate drug classes, or translational strategies were not available for extraction. - The editorial topic implies intersections among metabolic reprogramming in cancer cells, immune cell metabolism affecting antitumor responses, and opportunities to target metabolic-immune axes for therapy, but specific arguments or conclusions from the editorial were not present in the provided material. - For researchers and developers, the likely relevant areas would include metabolic enzymes, nutrient-sensing pathways, tumor microenvironment metabolites, and immune checkpoint-metabolism crosstalk; however, these were not described in the source and therefore cannot be asserted as findings from the editorial. - The absence of the editorial text in the supplied source means recommendations, prioritized targets, or discussed preclinical/clinical evidence were not reported and should be retrieved from the full article for implementation or citation.
## Clinical Analysis & Structured Key Points
Frontiers | Editorial: Cellular metabolism, the immune system, and oncogenesis: opportunities for drug discovery and development EDITORIAL article Front. Immunol. , 23 September 2026 Sec. Cancer Immunity and Immunotherapy Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1997905 Published in Frontiers in Immunology Cancer Immunity and Immunotherapy 7 impact factor 11.3 citescore Part of a Research Topic Cellular Metabolism, the Immune System, and Oncogenesis: Opportunities for Drug Discovery and Development 64k views 15 articles Editor & Reviewers Edited and reviewed by P B Peter Brossart Outline EDITORIAL article Front. Immunol. , 23 September 2026 Sec. Cancer Immunity and Immunotherapy Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1997905 Editorial: Cellular metabolism, the immune system, and oncogenesis: opportunities for drug discovery and development M N Monde Ntwasa 1 * E E Ekene Emmanuel Nweke 1,2,3 M K Mandeep Kaur 3,4 S S Selisha Sooklal 1 1. Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Florida, Roodepoort, South Africa 2. Department of Surgery, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa 3. Infectious Disease and Oncology Research Institute, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa 4. School of Molecular and Cell Biology, University of the Witwatersrand, Johannesburg, South Africa See more Article metrics View details Editorial on the Research Topic Cellular metabolism, the immune system, and oncogenesis: opportunities for drug discovery and development Nearly a century after Otto Warburg first described a unique phenomenon whereby tumour cells prefer the inefficient glycolytic pathway for energy generation ( 1 ), the phenomenon has continued to aid researchers in exploring the tumour ecosystem, including tumour initiation, progression and targeting. Furthermore, the Warburg effect has enabled researchers to interrogate how tumors and surrounding cells, such as immune and stromal cells, interact through shared and highly regulated metabolic processes. Tumor cells reprogram key metabolic processes, including glycolysis, lipid and amino acid processing, and nucleotide metabolism, to generate a “burst” of energy that fosters uncontrolled cellular proliferation ( 2 ). Deregulation of immune responses and metabolic processes has been recognized as a key hallmark of cancer ( 3 ). Similarly, immune cells have been observed to exhibit similar processes. For example, a T-cell mounting an effector response against a foreign body requires a similar energy “burst”. In addition, a regulatory T-cell would prefer to use the oxidative phosphorylation pathway ( 4 ). Therefore, the intricate tumor microenvironment has been described as a battleground with ongoing competition for metabolic resources. In this context, cancer cells often win this competition, starving immune cells of critical nutrients such as glucose and creating a lactate-acidified cellular environment that incapacitates the immune system ( 5 ). The goal is not simply to inhibit a tumor-intrinsic pathway, but to shift a competitive balance so that immune cells regain access to the resources they need to survive and function effectively. Consequently, immune cells usually undergo deregulated metabolism before immunologic deficiency. Cancer immunotherapy rests on the premise that the immune system can sufficiently recognize and kill tumor cells. Immunotherapeutic treatment must remove any impediment to this. For instance, checkpoint inhibitors work by releasing T cells and natural killer (NK) cells from inhibitory signals such as PD-1/PD-L1 and CTLA-4. Yet even where these therapies have improved outcomes, most patients with certain solid tumors still do not respond ( 6 ). Across cancer types, objective response rates to checkpoint blockade typically fall between 15% and 60%, with most solid tumors at the lower end and only melanoma and microsatellite-instability-high cancers approaching the upper end ( 7 ). A critical reason for this uneven outcome may be deregulated metabolism, reinforcing the relevance for drug discovery at the intersection of metabolism and immunity. One example showed that boosting a tumor’s own glycolysis is enough to override T cell control, but checkpoint blockade (anti-CTLA-4/PD-1/PD-L1) reverses this by restricting tumor glucose uptake, partly via PD-L1’s regulation of mTOR and glycolytic enzymes. As a result, glucose for T cells is freed up to fuel their glycolysis and IFN-γ production, showing that tumor-driven metabolic competition is a key mechanism of T cell dysfunction in cancer ( 8 ). Over the past several years, researchers have made concerted efforts to decipher the crucial links between the immune response and metabolic processes. One of these links, called the lactylation axis, was comprehensively described in the present collection, where the authors explained a lactate-mediated mechanistic bridge that enables post-translational modification of immune signaling proteins ( Tao et al. ). It was also demonstrated that in hepatocellular carcinoma, the lactate transporter MCT4 actively drives matrix metalloproteinase activation and polarizes tumor-associated macrophages toward an immunosuppressive M2 phenotype ( Zhang et al. ). These studies describe metabolism not as a downstream consequence of oncogenic mutation but as a targetable node, echoing several calls in published literature to move from descriptive immuno-onco-metabolism toward precision targeting ( 9 ). The papers in this collection span a wide range of malignancies and cover several metabolic pathways. In a study of acute myeloid leukemia, the authors showed that integrating transcriptomic data revealed substantial lipid metabolic heterogeneity across patient subgroups and highlighted GSTO1 as a potential therapeutic target within that heterogeneity ( Zhong et al. ). Another multi-omics analysis of ST3GAL4-mediated glycosphingolipid metabolism in triple-negative breast cancer linked this glycan-remodelling pathway to immune evasion and poorer prognosis ( Zhang et al. ). Researchers also investigated glucose metabolism, and one study showed that bile acid enrichment fuels aerobic glycolysis and immune evasion by stabilizing an FXR-RARα complex ( Jiang et al. ). The breadth of the collection’s scope, spanning glucose, amino acid, lipid, and adenosine metabolism, also reflects that there is no single master metabolic switch to flip in targeting cancer cells. For example, lipid metabolism now shapes dendritic cell function, macrophage polarization, and the exhaustion trajectory of tumor-infiltrating lymphocytes ( 10 , 11 ). Additionally, amino acid depletion, through arginase, tryptophan catabolism, and related pathways, remains one of the most direct mechanisms by which tumors disable adaptive immunity ( 12 , 13 ). Metabolic enzymes such as hexokinase, glutaminase, lactate dehydrogenase, and IDO are tractable drug targets, with established pharmacological inhibitors used to manage diseases such as diabetes, cardiovascular disease, and inflammatory diseases ( 14 ). Because tumor and immune metabolism are entangled, drugs that shift this metabolic balance can also improve the effectiveness of already approved immunotherapies, especially in previously non-responding patients, offering a lower-risk path to the clinic than de novo drug discovery ( 15 ). This has allowed metabolic pathway inhibitors to reach clinical testing faster than many oncogene-directed strategies. This collection offers instances of repurposing metabolic inhibitors for cancer. For example, Celecoxib, a drug developed for inflammation, was tested to prevent the malignant progression of smoking-induced lung tumors by suppressing COX-2/PGE2 signaling, a pathway associated with inflammation and metabolism ( Sakurai et al. ). In another study, Ailanthone, a natural compound, was found to induce apoptosis in osteosarcoma cells via endoplasmic reticulum stress, a mechanism increasingly recognized as intertwined with the lipid and protein-folding burdens carried by metabolically stressed tumor cells ( Zhang et al. ). However, metabolic pathways are shared. Consequently, a drug that starves a tumor of glutamine may just as easily starve the cytotoxic T cells sent to kill it ( 8 ). Therefore, a delicate balance must be maintained to ensure that immune cells still have sufficient energy to carry out their functions. Future research must focus on therapies that achieve this balance, ideally alongside existing immunotherapies, a goal this collection suggests is increasingly within reach. Conclusion This collection of primarily original research articles showcases how metabolic rewiring in cancer cells and the tumor microenvironment drives immune evasion, therapy resistance, and oncogenesis, while identifying novel metabolic and immunological targets for drug discovery. Key findings span lipid metabolism in leukemia, bile acid-driven glycolysis, lactylation-mediated immunosuppression, and machine learning-based biomarker discovery. Critical thematic areas include metabolic drivers, immune modulation, lipid pathways, biomarkers, and Drug Repurposing. These thematic areas offer opportunities to target metabolic enzymes and receptors, reverse immunosuppression by exploiting post-translational modifications such as lactylation, discover lipid metabolism inhibitors and diagnostic/prognostic tools, and repurpose agents in oncology, such as Celecoxib. Overall, these articles underscore that metabolic rewiring is not just a hallmark of cancer cells but a systemic driver of immune dysfunction, opening multiple avenues for drug development, including metabolic enzyme inhibitors and immunometabolism combination therapies. Statements Author contributions MN: Conceptualization, Formal analysis, Project administration, Validation, Writing – original draft, Writing – review & editing. EN: Formal analysis, Validation, Writing – original draft, Writing – review & editing. MK: Formal analysis, Validation, Writing – original draft, Writing – review & editing. SS: Writing – original draft, Writing – review & editing. Acknowledgments The guest editors wish to thank the Editorial Board of Frontiers in Immunology for providing the opportunity to edit this Special Issue, and Sophie Akopyan for their excellent and diligent assistance. We also thank all reviewers for their invaluable time and contributions. Conflict of interest The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Generative AI statement The author(s) declared that generative AI was not used in the creation of this manuscript. Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us. Publisher’s note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. 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( 2023 ) 28 : 103684 . doi: 10.1016/j.drudis.2023.103684 Pubmed Abstract CrossRef Google Scholar View reference in article Summary Keywords cancer , drug repurposing , immune checkpoint inhibitors , metabolic reprograming , tumour microenvironment Citation Ntwasa M, Nweke EE, Kaur M and Sooklal S (2026) Editorial: Cellular metabolism, the immune system, and oncogenesis: opportunities for drug discovery and development . Front. Immunol. 17:1997905. doi: 10.3389/fimmu.2026.1997905 Received 14 September 2026 Accepted 15 September 2026 Published 23 September 2026 Volume 17 - 2026 Edited and reviewed by Peter Brossart , University of Bonn, Bonn, Germany Updates Check for updates Copyright © 2026 Ntwasa, Nweke, Kaur and Sooklal. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. * Correspondence: Monde Ntwasa, ntwasmm@unisa.ac.za Disclaimer All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Article metrics View details Download PDF Download other formats ReadCube epub XML Cite article Share article Our quality Expert judgment makes science stronger Behind every published article stand expert reviewers safeguarding science. Discover our rigorous approach to peer review. Learn about peer review Outline Cite article Copy to clipboard Copy citation Export citation file BibTex EndNote Reference Manager Simple Text file Share article Facebook X LinkedIn Email WeChat Share on WeChat Scan with WeChat to share this article Article metrics
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