{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T08:58:33Z","timestamp":1790585913698,"version":"4.1.0"},"reference-count":145,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Immune checkpoint blockade (ICB) has revolutionized melanoma treatment, yet the in vivo ultrastructural consequences within the tumor microenvironment (TME) remain poorly characterized. This study investigates the morphological alterations induced by ICB at the peritumoral interface through a \u201credox storm\u201d paradigm. B16F10 melanoma-bearing mice were treated with anti-CTLA-4, anti-PD-1, or their combination, and evaluated by transmission electron microscopy (TEM) at Days 20, 30, and 40; quantitative morphometric analyses were performed for comparative purposes. This design enabled the assessment of ultrastructural changes from initial immune activation to late-stage remodeling, linking early cytotoxic events with subsequent stromal adaptations. TEM provided evidence of a sequential redox cascade characterized by lymphocyte reactivation, mitochondrial cristolysis, lipid droplet accumulation, foamy macrophage-like cells, efferocytosis-driven M2-like polarization, and metabolic plasticity in surviving tumor cells. Specifically, combination therapy was associated with marked cytolysis and extensive stromal remodeling, while anti-PD-1 appeared to promote prominent cholesterol crystal formation and lipotoxicity. Morphometric analyses supported these qualitative findings, indicating significant alterations in lipid droplet area and cell death area across treatment groups. This ultrastructural dissection provides morphological evidence for the \u201credox storm\u201d and offers a framework to understand ICB efficacy, resistance, and dynamic TME remodeling, ultimately providing a basis for targeted combination strategies.<\/jats:p>","DOI":"10.3390\/cells15191760","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T08:18:46Z","timestamp":1790583526000},"page":"1760","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Redox Storm in the Tumor Microenvironment (\u03a4\u039c\u0395): Multifaceted Redox Injury and Immunometabolic Reprogramming Induced by Immune Checkpoint Blockade in B16F10 Melanoma: An Ultrastructural Study of the Peritumoral Interface"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3719-4715","authenticated-orcid":false,"given":"Vasileios Alexandros","family":"Karakousis","sequence":"first","affiliation":[{"name":"School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"},{"name":"Laboratory of Histology-Embryology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"},{"name":"Department of Plastic Surgery, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Papageorgiou General Hospital, 56403 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Antonia","family":"Sioga","sequence":"additional","affiliation":[{"name":"Laboratory of Histology-Embryology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1459-9774","authenticated-orcid":false,"given":"Ioannis S.","family":"Vizirianakis","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"},{"name":"Department of Health Sciences, School of Life and Health Sciences, University of Nicosia, 1700 Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Isaak","family":"Kesisoglou","sequence":"additional","affiliation":[{"name":"School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Christophoros S.","family":"Kosmidis","sequence":"additional","affiliation":[{"name":"School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"},{"name":"Department of Surgery, European Interbalkan Medical Center, 57001 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5331-5634","authenticated-orcid":false,"given":"Leonidas","family":"Pavlidis","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Papageorgiou General Hospital, 56403 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0709-5407","authenticated-orcid":false,"given":"Theodora","family":"Papamitsou","sequence":"additional","affiliation":[{"name":"Laboratory of Histology-Embryology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Gosman, L.M., \u021a\u0103poi, D.-A., and Costache, M. (2023). Cutaneous Melanoma: A Review of Multifactorial Pathogenesis, Immunohistochemistry, and Emerging Biomarkers for Early Detection and Management. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242115881"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Waseh, S., and Lee, J.B. (2023). Advances in melanoma: Epidemiology, diagnosis, and prognosis. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1268479"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Caraviello, C., Nazzaro, G., Tavoletti, G., Boggio, F., Denaro, N., Murgia, G., Passoni, E., Benzecry Mancin, V., and Marzano, A.V. (2025). Melanoma Skin Cancer: A Comprehensive Review of Current Knowledge. Cancers, 17.","DOI":"10.3390\/cancers17172920"},{"key":"ref_4","first-page":"1005","article-title":"Melanoma: Epidemiology, risk factors, pathogenesis, diagnosis and classification","volume":"28","author":"Rastrelli","year":"2014","journal-title":"In Vivo"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kim, H.J., and Kim, Y.H. (2024). Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25052984"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Eddy, K., and Chen, S. (2020). Melanoma Subtypes and Their Molecular Abnormalities. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21238984"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s11912-026-01750-1","article-title":"Immune checkpoint inhibitors in malignant melanoma: Anti-PD-1, anti-CTLA-4 and anti-LAG-3 therapies","volume":"28","author":"Giannakis","year":"2026","journal-title":"Curr. Oncol. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1002\/eji.202048747","article-title":"Combined anti-PD-1 and anti-CTLA-4 checkpoint blockade: Treatment of melanoma and immune mechanisms of action","volume":"51","author":"Willsmore","year":"2021","journal-title":"Eur. J. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Azarov, I., Helmlinger, G., Kosinsky, Y., and Peskov, K. (2022). Elaborating on anti-CTLA-4 mechanisms of action using an agent-based modeling approach. Front. Appl. Math. Stat., 8.","DOI":"10.3389\/fams.2022.993581"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"ltaf008","DOI":"10.1093\/immadv\/ltaf008","article-title":"CTLA-4-two pathways to anti-tumour immunity?","volume":"5","author":"Ward","year":"2025","journal-title":"Immunother. Adv."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Liang, Y., Zheng, Y., Zeng, Y., Hu, C., Si, Y., Fan, X., and Chen, Q. (2025). Immune checkpoint inhibitors in melanoma: Mechanisms, immune cell interactions, and the tumour microenvironment. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1691608"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mehta, A., Motavaf, M., Nebo, I., Luyten, S., Osei-Opare, K.D., and Gru, A.A. (2025). Advancements in melanoma treatment: A review of PD-1 inhibitors, T-VEC, mRNA vaccines, and tumor-infiltrating lymphocyte therapy in an evolving landscape of immunotherapy. J. Clin. Med., 14.","DOI":"10.3390\/jcm14041200"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Karakousis, V.A., Mantalovas, S., Karakousi, V.C., Vizirianakis, I.S., Papamitsou, T., Pavlidis, L., and Kosmidis, C.S. (2026). Reshaping the Battlefield: Reprogramming the Melanoma Tumour Microenvironment (TME) by Anti-CTLA-4, Anti-PD-1, and Anti-PD-L1 Monotherapy and Combination Therapy: A Systematic Review and Meta-Analysis of Preclinical and Clinical Evidence. Cells, 15.","DOI":"10.3390\/cells15131182"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"14759","DOI":"10.18632\/oncotarget.14736","article-title":"Clinicopathological significance of intratumoral and peritumoral lymphocytes and lymphocyte score based on the histologic subtypes of cutaneous melanoma","volume":"8","author":"Park","year":"2017","journal-title":"Oncotarget"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Sabbatino, F., Scognamiglio, G., Liguori, L., Marra, A., Anniciello, A.M., Polcaro, G., Dal Col, J., Caputo, A., Peluso, A.L., and Botti, G. (2020). Peritumoral Immune Infiltrate as a Prognostic Biomarker in Thin Melanoma. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.561390"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lin, Z., Zou, S., and Wen, K. (2024). The crosstalk of CD8+ T cells and ferroptosis in cancer. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1255443"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41392-024-01769-5","article-title":"Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies","volume":"9","author":"Zhou","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2042","DOI":"10.1007\/s10495-025-02155-4","article-title":"Mitochondrial bioenergetics and networks in melanoma: An update","volume":"30","author":"Giannitti","year":"2025","journal-title":"Apoptosis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1021\/acschembio.5b00737","article-title":"Mitochondrial Redox Opto-Lipidomics Reveals Mono-Oxygenated Cardiolipins as Pro-Apoptotic Death Signals","volume":"11","author":"Mao","year":"2016","journal-title":"ACS Chem. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/j.devcel.2021.04.013","article-title":"Lipid metabolism in cancer: New perspectives and emerging mechanisms","volume":"56","author":"Broadfield","year":"2021","journal-title":"Dev. Cell"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Pascual, G., and Benitah, S.A. (2024). Lipids in the tumor microenvironment: Immune modulation and metastasis. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1435480"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Lang, C., Roy, S., Wang, Y., Graves, D., Xu, Y., Serezani, C.H., Korrer, M., and Kim, Y.J. (2022). Efferocytosis drives myeloid NLRP3 dependent inflammasome signaling secretion of IL-1\u03b2 to promote tumor growth. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.993771"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e14467","DOI":"10.1111\/acel.14467","article-title":"Efferocytosis: The Janus-Faced Gatekeeper of Aging and Tumor Fate","volume":"24","author":"Liu","year":"2025","journal-title":"Aging Cell"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Bleve, A., Durante, B., Sica, A., and Consonni, F.M. (2020). Lipid Metabolism and Cancer Immunotherapy: Immunosuppressive Myeloid Cells at the Crossroad. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165845"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.immuni.2016.09.016","article-title":"mTORC2-IRF4 mediated metabolic reprogramming is essential for macrophage alternative activation","volume":"45","author":"Huang","year":"2016","journal-title":"Immunity"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/pcmr.12661","article-title":"Metabolic strategies of melanoma cells: Mechanisms, interactions with the tumor microenvironment, and therapeutic implications","volume":"31","author":"Fischer","year":"2018","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5035","DOI":"10.1158\/0008-5472.CAN-12-0979","article-title":"Inactivation of the HIF-1\u03b1\/PDK3 signaling axis drives melanoma toward mitochondrial oxidative metabolism and potentiates the therapeutic activity of pro-oxidants","volume":"72","author":"Kluza","year":"2012","journal-title":"Cancer Res."},{"key":"ref_28","first-page":"4799","article-title":"A clinically relevant, syngeneic model of spontaneous, highly metastatic B16 mouse melanoma","volume":"30","author":"Bobek","year":"2010","journal-title":"Anticancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Overwijk, W.W., and Restifo, N.P. (2001). B16 as a mouse model for human melanoma. Curr. Protoc. Immunol., 39.","DOI":"10.1002\/0471142735.im2001s39"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"363","DOI":"10.18388\/abp.2012_2122","article-title":"Properties of B16-F10 murine melanoma cells subjected to metabolic stress conditions","volume":"59","author":"Mitrus","year":"2012","journal-title":"Acta Biochim. Pol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Lin, Z., Wan, Y., Cai, H., Deng, L., and Li, R. (2019). The Immunogenicity and Anti-tumor Efficacy of a Rationally Designed Neoantigen Vaccine for B16F10 Mouse Melanoma. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02472"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/1479-5876-5-20","article-title":"Therapy of established B16-F10 melanoma tumors by a single vaccination of CTL\/T helper peptides in VacciMax","volume":"5","author":"Mansour","year":"2007","journal-title":"J. Transl. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1177\/0023677217724823","article-title":"PREPARE: Guidelines for planning animal research and testing","volume":"52","author":"Smith","year":"2018","journal-title":"Lab. Anim."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.1111\/bph.15193","article-title":"The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research","volume":"177","author":"Hurst","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e00794","DOI":"10.1016\/j.btre.2023.e00794","article-title":"Therapeutic efficacy of plant-produced Nivolumab in transgenic C57BL\/6-hPD-1 mouse implanted with MC38 colon cancer","volume":"38","author":"Bulaon","year":"2023","journal-title":"Biotechnol. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1080\/1547691X.2020.1826020","article-title":"A T-cell-dependent antibody response study using a murine surrogate anti-PD-1 monoclonal antibody as an alternative to a non-human primate model","volume":"17","author":"Plitnick","year":"2020","journal-title":"J. Immunotoxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e000400","DOI":"10.1136\/jitc-2019-000400","article-title":"Poor outcome with anti-programmed death-ligand 1 (PD-L1) antibody due to poor pharmacokinetic properties in PD-1\/PD-L1 blockade-sensitive mouse models","volume":"8","author":"Kurino","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e001584","DOI":"10.1136\/jitc-2020-001584","article-title":"Antitumor efficacy of combined CTLA4\/PD-1 blockade without intestinal inflammation is achieved by elimination of Fc\u03b3R interactions","volume":"8","author":"Mauze","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e007433","DOI":"10.1136\/jitc-2023-007433","article-title":"Local and distant response to intratumoral immunotherapy assessed by immunoPET in mice","volume":"11","author":"Meyblum","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"7174","DOI":"10.1158\/1538-7445.AM2024-7174","article-title":"Pharmacokinetics and immunogenicity of anti-PD-1 antibody in humanized FcRn mouse models compared to immunocompetent mouse models","volume":"84","author":"Tu","year":"2024","journal-title":"Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Boch, C., Reschke, M., Igney, F., Maier, P., M\u00fcller, P., Danklmaier, S., Das, K., Hofer, T., Wollmann, G., and Rist, W. (2022). Evaluating Antibody Pharmacokinetics as Prerequisite for Determining True Efficacy as Shown by Dual Targeting of PD-1 and CD96. Biomedicines, 10.","DOI":"10.3390\/biomedicines10092146"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e1724751","DOI":"10.1080\/19420862.2020.1724751","article-title":"HX008: A humanized PD-1 blocking antibody with potent antitumor activity and superior pharmacologic properties","volume":"12","author":"Zhang","year":"2020","journal-title":"mAbs"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1002\/psp4.12800","article-title":"Quantitative Systems Pharmacology Modeling Provides Insight into Inter-Mouse Variability of Anti-CTLA4 Response","volume":"11","author":"Qiao","year":"2022","journal-title":"CPT Pharmacomet. Syst. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1038\/nm.4200","article-title":"Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses","volume":"22","author":"Moynihan","year":"2016","journal-title":"Nat. Med."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Persson, J., Beyer, I., Yumul, R., Li, Z., Kiem, H.-P., Roffler, S., and Lieber, A. (2011). Immuno-therapy with anti-CTLA4 antibodies in tolerized and non-tolerized mouse tumor models. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022303"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"101405","DOI":"10.1016\/j.tranon.2022.101405","article-title":"Anti-CTLA-4 and anti-PD-1 immunotherapies repress tumor progression in preclinical breast and colon model with independent regulatory T cells response","volume":"20","author":"Rupp","year":"2022","journal-title":"Transl. Oncol."},{"key":"ref_47","unstructured":"(2015). OPDIVO (Nivolumab) 10 mg\/mL Concentrate for Solution for Infusion: Summary of Product Characteristics, Bristol-Myers Squibb Pharma EEIG. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/opdivo-epar-product-information_en.pdf."},{"key":"ref_48","unstructured":"(2016). YERVOY (Ipilimumab) 5 mg\/mL Concentrate for Solution for Infusion: Summary of Product Characteristics, Bristol-Myers Squibb Pharma EEIG. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/yervoy-epar-product-information_en.pdf."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1002\/psp4.12130","article-title":"Translational Pharmacokinetic\/Pharmacodynamic Modeling of Tumor Growth Inhibition Supports Dose-Range Selection of the Anti-PD-1 Antibody Pembrolizumab","volume":"6","author":"Lindauer","year":"2017","journal-title":"CPT Pharmacomet. Syst. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12987-023-00420-9","article-title":"Morphological and mitochondrial changes in murine choroid plexus epithelial cells during healthy aging","volume":"20","author":"Scarpetta","year":"2023","journal-title":"Fluids Barriers CNS"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1038\/s42255-025-01367-x","article-title":"DDHD2 provides a flux of saturated fatty acids for neuronal energy and function","volume":"7","author":"Saber","year":"2025","journal-title":"Nat. Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e0350242024","DOI":"10.1523\/JNEUROSCI.0350-24.2024","article-title":"Brief and Diverse Excitotoxic Insults Increase the Neuronal Nuclear Membrane Permeability in the Neonatal Brain, Resulting in Neuronal Dysfunction and Cell Death","volume":"44","author":"Suryavanshi","year":"2024","journal-title":"J. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Joost, S., Schweiger, F., Pfeiffer, F., Ertl, C., Keiler, J., Frank, M., and Kipp, M. (2022). Cuprizone Intoxication Results in Myelin Vacuole Formation. Front. Cell. Neurosci., 16.","DOI":"10.3389\/fncel.2022.709596"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3627","DOI":"10.1016\/j.csbj.2023.07.010","article-title":"Rapid microbial viability assay using scanning electron microscopy: A proof-of-concept using Phosphotungstic acid staining","volume":"21","author":"Zmerli","year":"2023","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_56","unstructured":"JASP Team (JASP, 2026). JASP, Version 0.96.0.0; Computer Software."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1093\/biomet\/52.3-4.591","article-title":"An analysis of variance test for normality (complete samples)","volume":"52","author":"Shapiro","year":"1965","journal-title":"Biometrika"},{"key":"ref_58","unstructured":"Fisher, R.A. (1925). Statistical Methods for Research Workers, Oliver & Boyd."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"99","DOI":"10.2307\/3001913","article-title":"Comparing Individual Means in the Analysis of Variance","volume":"5","author":"Tukey","year":"1949","journal-title":"Biometrics"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1080\/01621459.1952.10483441","article-title":"Use of Ranks in One-Criterion Variance Analysis","volume":"47","author":"Kruskal","year":"1952","journal-title":"J. Am. Stat. Assoc."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1080\/00401706.1964.10490181","article-title":"Multiple Comparisons Using Rank Sums","volume":"6","author":"Dunn","year":"1964","journal-title":"Technometrics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"251","DOI":"10.4103\/0973-029X.99081","article-title":"Toluidine Blue: A Review of Its Chemistry and Clinical Utility","volume":"16","author":"Sridharan","year":"2012","journal-title":"J. Oral Maxillofac. Pathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4236\/mr.2014.21001","article-title":"Three-Dimensional Analysis of Melanosomes Isolated from B16 Melanoma Cells by Using Ultra High Voltage Electron Microscopy","volume":"2","author":"Akazaki","year":"2014","journal-title":"Microsc. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"745","DOI":"10.3390\/clockssleep4040056","article-title":"Characteristic of Ultrastructure of Mice B16 Melanoma Cells under the Influence of Different Lighting Regimes","volume":"4","author":"Areshidze","year":"2022","journal-title":"Clocks Sleep"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Gao, R., Zhang, X., Zou, K., Meng, D., and Lv, J. (2023). Cryptochrome 1 activation inhibits melanogenesis and melanosome transport through negative regulation of cAMP\/PKA\/CREB signaling pathway. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1081030"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"17099","DOI":"10.1073\/pnas.1113703108","article-title":"CD4+ T-cell synapses involve multiple distinct stages","volume":"108","author":"Ueda","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e70239","DOI":"10.1002\/jev2.70239","article-title":"T-Cell-Derived Exosomes From Multi Core Granules Exhibit Superior Caspase-3-Mediated Tumor-Suppressive Activity Compared to Those From Multivesicular Bodies","volume":"15","author":"Alawar","year":"2026","journal-title":"J. Extracell. Vesicles"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Santucci, P., Bouzid, F., Smichi, N., Poncin, I., Kremer, L., De Chastellier, C., Drancourt, M., and Canaan, S. (2016). Experimental Models of Foamy Macrophages and Approaches for Dissecting the Mechanisms of Lipid Accumulation and Consumption during Dormancy and Reactivation of Tuberculosis. Front. Cell. Infect. Microbiol., 6.","DOI":"10.3389\/fcimb.2016.00122"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Rajam\u00e4ki, K., Lappalainen, J., \u00d6\u00f6rni, K., V\u00e4lim\u00e4ki, E., Matikainen, S., Kovanen, P.T., and Eklund, K.K. (2010). Cholesterol Crystals Activate the NLRP3 Inflammasome in Human Macrophages: A Novel Link between Cholesterol Metabolism and Inflammation. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011765"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e004381","DOI":"10.1136\/jitc-2021-004381","article-title":"Nanoparticle delivery of miR-21-3p sensitizes melanoma to anti-PD-1 immunotherapy by promoting ferroptosis","volume":"10","author":"Guo","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e008554","DOI":"10.1136\/jitc-2023-008554","article-title":"Mefloquine enhances the efficacy of anti-PD-1 immunotherapy via IFN-\u03b3-STAT1-IRF1-LPCAT3-induced ferroptosis in tumors","volume":"12","author":"Tao","year":"2024","journal-title":"J. Immunother. Cancer"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1016\/j.ymthe.2021.03.013","article-title":"Inhibition of xCT suppresses the efficacy of anti-PD-1\/L1 melanoma treatment through exosomal PD-L1-induced macrophage M2 polarization","volume":"29","author":"Liu","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Tuerxun, H., Zhao, Y., Li, Y., Liu, X., Wen, S., and Zhao, Y. (2025). Resveratrol alleviates testicular toxicity induced by anti-PD-1 through regulating the NRF2-SLC7A11-GPX4 pathway. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1529991"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1186\/s13046-025-03521-5","article-title":"Vinburnine potentiates anti-PD1 immunotherapy in melanoma through IL-24 secretion via P38\/MAPK\/ATF3 signaling","volume":"44","author":"Zhu","year":"2025","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s13046-025-03378-8","article-title":"Metabolomic signatures in liquid biopsy are associated with overall survival in metastatic melanoma patients treated with immune checkpoint inhibitor therapy","volume":"44","author":"Costantini","year":"2025","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.2217\/imt-2016-0083","article-title":"Use of LDH and autoimmune side effects to predict response to ipilimumab treatment","volume":"8","author":"Dick","year":"2016","journal-title":"Immunotherapy"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1038\/s41416-018-0167-x","article-title":"S100B and LDH as early prognostic markers for response and overall survival in melanoma patients treated with anti-PD-1 or combined anti-PD-1 plus anti-CTLA-4 antibodies","volume":"119","author":"Wagner","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Chen, K., Zhu, F., Li, X., and Yoshimura, T. (2026). Advances in Immune Checkpoint Inhibitors for Cancer Treatment. Cancers, 18.","DOI":"10.3390\/cancers18111804"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s12943-025-02294-x","article-title":"Dual role of interferon-gamma in the response of melanoma patients to immunotherapy with immune checkpoint inhibitors","volume":"24","author":"Wawrzyniak","year":"2025","journal-title":"Mol. Cancer"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41467-024-54791-0","article-title":"Remodelling of the immune landscape by IFN\u03b3 counteracts IFN\u03b3-dependent tumour escape in mouse tumour models","volume":"16","author":"Lau","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Cai, H., Ren, Y., Chen, S., Wang, Y., and Chu, L. (2023). Ferroptosis and tumor immunotherapy: A promising combination therapy for tumors. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1119369"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1186\/s12967-024-05134-6","article-title":"CD8+ T cell-based cancer immunotherapy","volume":"22","author":"Chen","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1186\/s12943-026-02590-0","article-title":"Ferroptosis as a therapeutic target in cancer: Mechanisms, immune interactions, and emerging strategies","volume":"25","author":"Tang","year":"2026","journal-title":"Mol. Cancer"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1002\/cac2.12250","article-title":"Ferroptosis in cancer and cancer immunotherapy","volume":"42","author":"Zhao","year":"2022","journal-title":"Cancer Commun."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1038\/s41419-024-07244-x","article-title":"Emerging mechanisms of lipid peroxidation in regulated cell death and its physiological implications","volume":"15","author":"Zheng","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"100049","DOI":"10.1016\/j.clnves.2025.100049","article-title":"Targeting ferroptosis in cancer therapy: Mechanisms, strategies, and clinical applications","volume":"1","author":"Dai","year":"2025","journal-title":"Cell Investig."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s00018-025-05982-5","article-title":"Ferroptosis and cancer: When iron turns against tumors","volume":"83","author":"Toyokuni","year":"2025","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/s41420-024-01825-7","article-title":"Ferroptosis: Emerging mechanisms, biological function, and therapeutic potential in cancer and inflammation","volume":"10","author":"Jin","year":"2024","journal-title":"Cell Death Discov."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s13046-023-02925-5","article-title":"Modulating ferroptosis sensitivity: Environmental and cellular targets within the tumor microenvironment","volume":"43","author":"Hua","year":"2024","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1007\/s00262-025-04109-w","article-title":"T cell-derived small extracellular vesicles in cancer-immune interactions","volume":"74","author":"Garcia","year":"2025","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Pizzimenti, S., Ribero, S., Cucci, M.A., Grattarola, M., Monge, C., Dianzani, C., Barrera, G., and Muzio, G. (2021). Oxidative Stress-Related Mechanisms in Melanoma and in the Acquired Resistance to Targeted Therapies. Antioxidants, 10.","DOI":"10.3390\/antiox10121942"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Aboelella, N.S., Brandle, C., Kim, T., Ding, Z.-C., and Zhou, G. (2021). Oxidative Stress in the Tumor Microenvironment and Its Relevance to Cancer Immunotherapy. Cancers, 13.","DOI":"10.3390\/cancers13050986"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Allegra, A., Murdaca, G., Mirabile, G., and Gangemi, S. (2023). Redox Signaling Modulates Activity of Immune Checkpoint Inhibitors in Cancer Patients. Biomedicines, 11.","DOI":"10.3390\/biomedicines11051325"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Cheng, X., Wang, Y., Johnson, B., and You, M. (2025). Mitochondria-targeted strategies in tumor immunity. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1646138"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Chattopadhyay, A., Jagdish, S., Karhale, A.K., Ramteke, N.S., Zaib, A., and Nandi, D. (2023). IFN-\u03b3 lowers tumor growth by increasing glycolysis and lactate production in a nitric oxide-dependent manner: Implications for cancer immunotherapy. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1282653"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1111\/cas.70388","article-title":"Multifunctional Role of Mitochondrial Fatty Acid Oxidation in Cancer Immunotherapy and Aging","volume":"117","author":"Kitaoka","year":"2026","journal-title":"Cancer Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s12944-024-02024-0","article-title":"Reprogramming of lipid metabolism in the tumor microenvironment: A strategy for tumor immunotherapy","volume":"23","author":"Wu","year":"2024","journal-title":"Lipids Health Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2414495","DOI":"10.1002\/adfm.202414495","article-title":"Highly Efficient and Universal Degradation of PD-L1 via Mitochondrial Oxidative Stress Evoked by Cationic AIE-Active Photosensitizers for Cancer Immunotherapy","volume":"35","author":"Liu","year":"2025","journal-title":"Adv. Funct. Mater."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"218457","DOI":"10.1016\/j.canlet.2026.218457","article-title":"Melanoma cells release dysfunctional mitochondria to the tumor microenvironment and circulation in association with tumor progression","volume":"647","author":"Fuentes","year":"2026","journal-title":"Cancer Lett."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3727\/096504016X14550280421449","article-title":"Plasmid-Based Stat3 siRNA Delivered by Functional Graphene Oxide Suppresses Mouse Malignant Melanoma Cell Growth","volume":"23","author":"Yin","year":"2016","journal-title":"Oncol. Res."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Catalani, E., Giovarelli, M., Zecchini, S., Perrotta, C., and Cervia, D. (2021). Oxidative Stress and Autophagy as Key Targets in Melanoma Cell Fate. Cancers, 13.","DOI":"10.3390\/cancers13225791"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"101617","DOI":"10.1016\/j.jbc.2022.101617","article-title":"Metabolic regulation of ferroptosis in the tumor microenvironment","volume":"298","author":"Mbah","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nchembio.2238","article-title":"Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis","volume":"13","author":"Kagan","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.1158\/0008-5472.CAN-25-0840","article-title":"DGAT1 Inhibition Induces Ferroptosis and Enhances Cancer Immunotherapy Efficacy","volume":"86","author":"Pan","year":"2026","journal-title":"Cancer Res."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Wang, W., Li, H., Liang, S., Hu, Y., Ding, J., Wu, X., and Hua, D. (2025). Bridging the gap: Ferroptosis of immune cells in the tumor microenvironment. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1648432"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Xiao, L., Xian, M., Zhang, C., Guo, Q., and Yi, Q. (2024). Lipid peroxidation of immune cells in cancer. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1322746"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Xiong, L., and Cheng, J. (2025). Rewiring lipid metabolism to enhance immunotherapy efficacy in melanoma: A frontier in cancer treatment. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1519592"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.cmet.2018.02.015","article-title":"High Cholesterol at the Heart of Phagolysosomal Damage","volume":"27","author":"Lieberman","year":"2018","journal-title":"Cell Metab."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1126\/science.aan4183","article-title":"Defective Cholesterol Clearance Limits Remyelination in the Aged Central Nervous System","volume":"359","author":"Fitzner","year":"2018","journal-title":"Science"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"6307","DOI":"10.1016\/j.apsb.2025.09.043","article-title":"Ferroptosis meets cancer immunotherapy: Overcoming the crosstalk challenges through advanced drug delivery strategies","volume":"15","author":"Gan","year":"2025","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"e001408","DOI":"10.1136\/jitc-2020-001408","article-title":"Phagocytic function of tumor-associated macrophages as a key determinant of tumor progression control: A review","volume":"8","author":"Lecoultre","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"115540","DOI":"10.1016\/j.biopha.2023.115540","article-title":"Efferocytosis: An accomplice of cancer immune escape","volume":"167","author":"Qiu","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e70601","DOI":"10.1002\/ctm2.70601","article-title":"Metabolic reprogramming of efferocytosis in the tumour microenvironment: From apoptotic-cell clearance to therapeutic targeting","volume":"16","author":"Yang","year":"2026","journal-title":"Clin. Transl. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2006220","DOI":"10.1002\/adfm.202006220","article-title":"Macrophage-Mediated Tumor Cell Phagocytosis: Opportunity for Nanomedicine Intervention","volume":"31","author":"Zhou","year":"2022","journal-title":"Adv. Funct. Mater."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1146\/annurev-immunol-042617-053010","article-title":"Apoptosis and Clearance of Apoptotic Cells","volume":"36","author":"Nagata","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"eado8366","DOI":"10.1126\/sciadv.ado8366","article-title":"MerTK+ macrophages promote melanoma progression and immunotherapy resistance through AhR-ALKAL1 activation","volume":"10","author":"Wu","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Asare, P.F., Roscioli, E., Hurtado, P.R., Tran, H.B., Mah, C.Y., and Hodge, S. (2020). LC3-Associated Phagocytosis (LAP): A Potentially Influential Mediator of Efferocytosis-Related Tumor Progression and Aggressiveness. Front. Oncol., 10.","DOI":"10.3389\/fonc.2020.01298"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1007\/s10495-017-1413-z","article-title":"The immune response to secondary necrotic cells","volume":"22","author":"Sachet","year":"2017","journal-title":"Apoptosis"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"18089","DOI":"10.1021\/acsnano.3c04884","article-title":"Efferocytosis Nanoinhibitors to Promote Secondary Necrosis and Potentiate the Immunogenicity of Conventional Cancer Therapies for Improved Therapeutic Benefits","volume":"17","author":"Wu","year":"2023","journal-title":"ACS Nano"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Ceci, C., Atzori, M.G., Lacal, P.M., and Graziani, G. (2020). Targeting Tumor-Associated Macrophages to Increase the Efficacy of Immune Checkpoint Inhibitors: A Glimpse into Novel Therapeutic Approaches for Metastatic Melanoma. Cancers, 12.","DOI":"10.3390\/cancers12113401"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s13045-024-01559-0","article-title":"Deciphering the performance of macrophages in tumour microenvironment: A call for precision immunotherapy","volume":"17","author":"Toledo","year":"2024","journal-title":"J. Hematol. Oncol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"18486","DOI":"10.18632\/oncotarget.14474","article-title":"Targeting macrophage anti-tumor activity to suppress melanoma progression","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1016\/j.apsb.2022.10.027","article-title":"The impact of lipids on the cancer-immunity cycle and strategies for modulating lipid metabolism to improve cancer immunotherapy","volume":"13","author":"Zheng","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"13130","DOI":"10.1038\/ncomms13130","article-title":"Polarization of M2 macrophages requires Lamtor1 that integrates cytokine and amino-acid signals","volume":"7","author":"Kimura","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.immuni.2009.06.018","article-title":"Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR","volume":"31","author":"Bensinger","year":"2009","journal-title":"Immunity"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1073\/pnas.1612920114","article-title":"COX2\/mPGES1\/PGE2 pathway regulates PD-L1 expression in tumor-associated macrophages and myeloid-derived suppressor cells","volume":"114","author":"Prima","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"110914","DOI":"10.1016\/j.celrep.2022.110914","article-title":"PGE2-EP2\/EP4 signaling elicits immunosuppression by driving the mregDC-Treg axis in inflammatory tumor microenvironment","volume":"39","author":"Thumkeo","year":"2022","journal-title":"Cell Rep."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Huang, C., Radi, R.H., and Arbiser, J.L. (2021). Mitochondrial Metabolism in Melanoma. Cells, 10.","DOI":"10.3390\/cells10113197"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1111\/pcmr.12579","article-title":"Hypoxia-induced HIF1\u03b1 targets in melanocytes reveal a molecular profile associated with poor melanoma prognosis","volume":"30","author":"Loftus","year":"2017","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/s41420-025-02617-3","article-title":"Metabolic reprogramming in melanoma therapy","volume":"11","author":"Shen","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1017\/erm.2026.10044","article-title":"Hypoxia and HIF signalling in tumour microenvironment: Linking immune evasion, metabolic rewiring and epigenetic regulation","volume":"28","author":"Ameer","year":"2026","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e70065","DOI":"10.1002\/mog2.70065","article-title":"Oxidative Stress and DNA Epigenetic Modifications in Cancer: Mechanisms and Targeted Therapeutics","volume":"5","author":"Yang","year":"2026","journal-title":"MedComm Oncol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/s41420-025-02683-7","article-title":"The ATF4-glutamine axis: A central node in cancer metabolism, stress adaptation, and therapeutic targeting","volume":"11","author":"Yan","year":"2025","journal-title":"Cell Death Discov."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Foglia, B., Nurcis, J., Signorini, M., and Cannito, S. (2026). Tumor-immune metabolic tug-of-war: From immune escape to targeting metabolic rewiring in cancer therapy. Front. Cell Dev. Biol., 14.","DOI":"10.3389\/fcell.2026.1823145"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Zhao, Z., Mei, Y., Wang, Z., and He, W. (2023). The Effect of Oxidative Phosphorylation on Cancer Drug Resistance. Cancers, 15.","DOI":"10.3390\/cancers15010062"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1038\/s41591-025-03699-3","article-title":"Inherited mitochondrial genetics as a predictor of immune checkpoint inhibition efficacy in melanoma","volume":"31","author":"Monson","year":"2025","journal-title":"Nat. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s13045-026-01780-z","article-title":"The distinct roles of ROS in tumor immunity: From mechanisms to immunotherapeutic applications","volume":"19","author":"Li","year":"2026","journal-title":"J. Hematol. Oncol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/s41392-026-02583-x","article-title":"Reactive oxygen species (ROS) in cancer: From mechanism to therapeutic implications","volume":"11","author":"Akter","year":"2026","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"105168","DOI":"10.1016\/j.critrevonc.2026.105168","article-title":"ROS-mediated therapeutic approach through oxidative stress and cell signalling modulation","volume":"220","author":"Sahu","year":"2026","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"De Melo, V.C., Sales, G.S., Moura, J.L.N., Bagatini, M.D., and Silva, G.B. (2026). Resistance to Anti-PD-1 Immunotherapy in Cutaneous Melanoma: The Role of Mitochondrial Metabolism and Therapeutic Perspectives. Clin. Bioenerg., 2.","DOI":"10.3390\/clinbioenerg2020008"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"3535","DOI":"10.1158\/0008-5472.CAN-13-2893-T","article-title":"Targeting mitochondrial oxidative metabolism in melanoma causes metabolic compensation through glucose and glutamine utilization","volume":"74","author":"Lim","year":"2014","journal-title":"Cancer Res."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1158\/2767-9764.CRC-25-0357","article-title":"Autologous Thymic Organoids Support Functional T-cell Education and Enhance Antitumor Immunity in Humanized Mice with Melanoma Xenografts","volume":"5","author":"Morton","year":"2025","journal-title":"Cancer Res. Commun."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"37950","DOI":"10.1038\/s41598-025-20253-w","article-title":"NT-17, a novel long-acting interleukin-7, promotes anti-PD-1 efficacy in an autologous humanized melanoma model","volume":"15","author":"Phoon","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"306","DOI":"10.18632\/oncotarget.28880","article-title":"DHHC3 interferes with antitumor immunity in melanoma cells","volume":"17","author":"Sharma","year":"2026","journal-title":"Oncotarget"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"e54127","DOI":"10.15252\/embr.202154127","article-title":"Cell Communication Network factor 4 promotes tumor-induced immunosuppression in melanoma","volume":"23","author":"Fernandez","year":"2022","journal-title":"EMBO Rep."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/19\/1760\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T08:30:47Z","timestamp":1790584247000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/19\/1760"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,27]]},"references-count":145,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["cells15191760"],"URL":"https:\/\/doi.org\/10.3390\/cells15191760","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,27]]}}}