{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T18:12:35Z","timestamp":1788545555605,"version":"build-2803163510"},"reference-count":83,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Joan C. Edwards School of Medicine at Marshall University","award":["#124188"],"award-info":[{"award-number":["#124188"]}]},{"award":["#124188"],"award-info":[{"award-number":["#124188"]}],"id":[{"id":"https:\/\/ror.org\/02erqft81","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Institute of General Medical Sciences of the National Institutes of Health","award":["P20GM103434"],"award-info":[{"award-number":["P20GM103434"]}]},{"award":["P20GM103434"],"award-info":[{"award-number":["P20GM103434"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Monocarboxylate transporter 2 (MCT2; SLC16A7) is a high-affinity pyruvate transporter implicated in cancer metabolism. However, its role in lung cancer progression and the tumor microenvironment remains unclear. This study examined the effects of MCT2 reduction on tumor growth and cell-type-specific transcriptional changes within the tumor microenvironment. MCT2 loxP\/loxP mice were crossed with mCre-Tg mice, and MCT2 deletion was induced by tamoxifen. Control (CO) mice received vehicle treatment. TC1 cells (100,000 cells\/mouse) were injected subcutaneously, and tumors were harvested after 24 days. Single-nucleus RNA sequencing (snRNA-seq) was performed on isolated tumor nuclei (4000 nuclei\/sample; n = 3 per group) using the 10x Genomics Chromium platform. Data were processed with Cell Ranger v3.0.2 and Seurat v5.2.1, followed by differential expression and pathway enrichment analyses integrated with macrophage bulk RNA-seq data. Tumors in mice with systemic MCT2 reduction grew significantly faster than those in control mice, demonstrating an association between host MCT2 reduction and increased tumor growth. Transcriptomic analysis generated high-quality profiles from 6864 CO and 10,055 KO nuclei. Clustering identified 12 cellular populations and cell types. MCT2 reduction altered pathways involved in glycolysis, the tricarboxylic acid cycle, oxidative phosphorylation, and fatty acid metabolism across multiple populations. Macrophages showed prominent transcriptional changes, including enrichment of MAPK, PI3K-Akt, IgSF-CAM, ECM, and cytokine\u2013cytokine signaling pathways. These findings were supported by macrophage bulk RNA-seq data. Systemic MCT2 reduction was associated with increased tumor growth and broad transcriptional alterations within the tumor micro-environment. Differences in metabolic and immune-related transcriptional programs, particularly in macrophages, identify potential mechanisms associated with tumor progression that warrant further functional investigation.<\/jats:p>","DOI":"10.3390\/ijms27177819","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"7819","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Monocarboxylate Transporter 2 (MCT2) Reduction Is Associated with Increased Lung Tumor Growth and Alterations in the Immune Microenvironment in a Subcutaneous Tumor Model"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3345-9614","authenticated-orcid":false,"given":"Yen On","family":"Chan","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Zhuanhong","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Trupti","family":"Joshi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Joan C. 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Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5811-5148","authenticated-orcid":false,"given":"Abdelnaby","family":"Khalyfa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV 25755, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41568-018-0081-9","article-title":"The lung microenvironment: An important regulator of tumour growth and metastasis","volume":"19","author":"Altorki","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nrclinonc.2016.217","article-title":"Tumour-associated macrophages as treatment targets in oncology","volume":"14","author":"Mantovani","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13046-022-02272-x","article-title":"Tumor-associated macrophages in cancer: Recent advancements in cancer nanoimmunotherapies","volume":"41","author":"Kumari","year":"2022","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Khalyfa, A., Qiao, Z., Raju, M., Shyu, C.R., Coghill, L., Ericsson, A., and Gozal, D. (2021). Monocarboxylate Transporter-2 Expression Restricts Tumor Growth in a Murine Model of Lung Cancer: A Multi-Omic Analysis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910616"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.bbrc.2019.10.162","article-title":"Hypoxic adipocytes induce macrophages to release inflammatory cytokines that render skeletal muscle cells insulin resistant","volume":"521","author":"Zhang","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1124\/pr.119.018762","article-title":"Monocarboxylate Transporters (SLC16): Function, Regulation, and Role in Health and Disease","volume":"72","author":"Felmlee","year":"2020","journal-title":"Pharmacol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"107906","DOI":"10.1016\/j.jbc.2024.107906","article-title":"Glycolysis: A multifaceted metabolic pathway and signaling hub","volume":"300","author":"Kierans","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"eadn4508","DOI":"10.1126\/sciadv.adn4508","article-title":"Lactate transported by MCT1 plays an active role in promoting mitochondrial biogenesis and enhancing TCA flux in skeletal muscle","volume":"10","author":"Zhang","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.molmet.2019.07.006","article-title":"Monocarboxylate transporters in cancer","volume":"33","author":"Payen","year":"2020","journal-title":"Mol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/iub.572","article-title":"The monocarboxylate transporter family--role and regulation","volume":"64","author":"Halestrap","year":"2012","journal-title":"IUBMB Life"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4421","DOI":"10.1111\/bph.70110","article-title":"Role of monocarboxylate transporters in cancer immunology and their therapeutic potential","volume":"182","author":"Faghihkhorasani","year":"2025","journal-title":"Br. J. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9814","DOI":"10.1038\/s41598-018-28249-5","article-title":"Utilization of lactic acid in human myotubes and interplay with glucose and fatty acid metabolism","volume":"8","author":"Lund","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"104944","DOI":"10.1016\/j.nbd.2020.104944","article-title":"MCT2 overexpression rescues metabolic vulnerability and protects retinal ganglion cells in two models of glaucoma","volume":"141","author":"Pappenhagen","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1080\/19768354.2021.1915379","article-title":"MCT2 overexpression promotes recovery of cognitive function by increasing mitochondrial biogenesis in a rat model of stroke","volume":"25","author":"Yu","year":"2021","journal-title":"Anim. Cells Syst."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1248\/bpb.b23-00860","article-title":"Monocarboxylate Transporters 1 and 2 Are Responsible for L-Lactate Uptake in Differentiated Human Neuroblastoma SH-SY5Y Cells","volume":"47","author":"Sakuma","year":"2024","journal-title":"Biol. Pharm. Bull."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13059-020-1926-6","article-title":"Eleven grand challenges in single-cell data science","volume":"21","author":"Lahnemann","year":"2020","journal-title":"Genome Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"957","DOI":"10.2147\/CMAR.S421771","article-title":"Role of Human Monocarboxylate Transporter 1 (hMCT1) and 4 (hMCT4) in Tumor Cells and the Tumor Microenvironment","volume":"15","author":"Liu","year":"2023","journal-title":"Cancer Manag. Res."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Khalyfa, A., Warren, W., Andrade, J., Bottoms, C.A., Rice, E.S., Cortese, R., Kheirandish-Gozal, L., and Gozal, D. (2020). Transcriptomic Changes of Murine Visceral Fat Exposed to Intermittent Hypoxia at Single Cell Resolution. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22010261"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.cell.2017.04.014","article-title":"Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses","volume":"169","author":"Lavin","year":"2017","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Wang, J., Jiang, B., Deng, M., Yan, H., Zhang, P., Jin, W., and Shen, Z. (2025). Single-cell atlas of the tumor immune microenvironment across syngeneic murine models. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1676581"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2015.12.006","article-title":"The Emerging Hallmarks of Cancer Metabolism","volume":"23","author":"Pavlova","year":"2016","journal-title":"Cell Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.cmet.2022.01.007","article-title":"The hallmarks of cancer metabolism: Still emerging","volume":"34","author":"Pavlova","year":"2022","journal-title":"Cell Metab."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-cellbio-092910-154237","article-title":"Aerobic glycolysis: Meeting the metabolic requirements of cell proliferation","volume":"27","author":"Lunt","year":"2011","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1213\/ANE.0000000000007096","article-title":"Links Between Cellular Energy Metabolism and Pain Sensation","volume":"140","author":"Li","year":"2025","journal-title":"Anesth. Analg."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Min, J.W., Kim, W.J., Han, J.A., Jung, Y.J., Kim, K.T., Park, W.Y., Lee, H.O., and Choi, S.S. (2015). Identification of Distinct Tumor Subpopulations in Lung Adenocarcinoma via Single-Cell RNA-seq. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135817"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1038\/s41467-020-16334-1","article-title":"Cooperative transport mechanism of human monocarboxylate transporter 2","volume":"11","author":"Zhang","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.immuni.2019.12.011","article-title":"Top 10 Challenges in Cancer Immunotherapy","volume":"52","author":"Hegde","year":"2020","journal-title":"Immunity"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s13402-026-01186-6","article-title":"Lactate signaling and immune suppression in tumors: Mechanisms and therapeutic implications","volume":"49","author":"Wang","year":"2026","journal-title":"Cell Oncol."},{"key":"ref_34","first-page":"4811","article-title":"Macrophage transcriptome modification induced by hypoxia and lactate","volume":"18","author":"Zhao","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00262-026-04353-8","article-title":"Multi-omics study on tumor-associated macrophages remodeling the tumor microenvironment via the CXCL5-CXCR2 axis to drive immune escape in bladder cancer","volume":"75","author":"Jiang","year":"2026","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wang, X., Xiong, D., Cui, S., Duan, B., Ding, G., Huang, Y., and Wang, Q. (2026). Artificial intelligence-enabled multi-omics biomarkers for immune checkpoint blockade: Mechanisms, predictive modeling, and clinical translation. Front. Immunol., 17.","DOI":"10.3389\/fimmu.2026.1732079"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1002297","DOI":"10.37349\/etat.2025.1002297","article-title":"Metabolic mechanisms of immunotherapy resistance","volume":"6","year":"2025","journal-title":"Explor. Target. Antitumor Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature13110","article-title":"Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides","volume":"508","author":"Birsoy","year":"2014","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1038\/s41419-024-06808-1","article-title":"Glucose deprivation triggers DCAF1-mediated inactivation of Rheb-mTORC1 and promotes cancer cell survival","volume":"15","author":"Li","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"16027","DOI":"10.1038\/ncomms16027","article-title":"Nanopore long-read RNAseq reveals widespread transcriptional variation among the surface receptors of individual B cells","volume":"8","author":"Byrne","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Tang, J.X., Thompson, K., Taylor, R.W., and Olahova, M. (2020). Mitochondrial OXPHOS Biogenesis: Co-Regulation of Protein Synthesis, Import, and Assembly Pathways. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21113820"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s10863-012-9428-1","article-title":"Role of monocarboxylate transporters in human cancers: State of the art","volume":"44","author":"Pinheiro","year":"2012","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tibs.2015.12.001","article-title":"The Warburg Effect: How Does it Benefit Cancer Cells?","volume":"41","author":"Liberti","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nature13490","article-title":"Functional polarization of tumour-associated macrophages by tumour-derived lactic acid","volume":"513","author":"Colegio","year":"2014","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e70372","DOI":"10.1002\/mco2.70372","article-title":"Polarization of Tumor Cells and Tumor-Associated Macrophages: Molecular Mechanisms and Therapeutic Targets","volume":"6","author":"Wei","year":"2025","journal-title":"MedComm"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"115332","DOI":"10.1016\/j.ejca.2025.115332","article-title":"Immunometabolism of tumor-associated macrophages: A therapeutic perspective","volume":"220","author":"Karimova","year":"2025","journal-title":"Eur. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1007\/s12672-025-03258-9","article-title":"Advances in the regulation of macrophage polarization by the tumor microenvironment","volume":"16","author":"Peng","year":"2025","journal-title":"Discov. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e01238","DOI":"10.1002\/advs.202501238","article-title":"NDRG1-Driven Lactate Accumulation Promotes Lung Adenocarcinoma Progression Through the Induction of an Immunosuppressive Microenvironment","volume":"12","author":"Wu","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_49","first-page":"13413","article-title":"Influence of lactate in resistance to anti-PD-1\/PD-L1 therapy: Mechanisms and clinical applications (Review)","volume":"31","author":"Zeng","year":"2025","journal-title":"Mol. Med. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e70028","DOI":"10.1111\/1759-7714.70028","article-title":"ACT001 Suppresses the Malignant Progression of Small-Cell Lung Cancer by Inhibiting Lactate Production and Promoting Anti-Tumor Immunity","volume":"16","author":"Ding","year":"2025","journal-title":"Thorac. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e39371","DOI":"10.1097\/MD.0000000000039371","article-title":"Prognostic value of a lactate metabolism gene signature in lung adenocarcinoma and its associations with immune checkpoint blockade therapy response","volume":"103","author":"Huang","year":"2024","journal-title":"Medicine"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"103209","DOI":"10.1016\/j.redox.2024.103209","article-title":"Lactate-induced activation of tumor-associated fibroblasts and IL-8-mediated macrophage recruitment promote lung cancer progression","volume":"74","author":"Gu","year":"2024","journal-title":"Redox Biol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Shang, S., Wang, M.Z., Xing, Z., He, N., and Li, S. (2022). Lactate regulators contribute to tumor microenvironment and predict prognosis in lung adenocarcinoma. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1024925"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"217728","DOI":"10.1016\/j.canlet.2025.217728","article-title":"SENP1-Sirt3 axis promotes cholesterol biosynthesis in tumor-associated macrophages to suppress anti-tumor immunity","volume":"623","author":"Peng","year":"2025","journal-title":"Cancer Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"218410","DOI":"10.1016\/j.canlet.2026.218410","article-title":"FAP(+) fibroblasts promote C1QC(+) macrophage infiltration via WNT2 signaling to exacerbate T cell exhaustion in oral squamous cell carcinoma","volume":"646","author":"Chen","year":"2026","journal-title":"Cancer Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"217272","DOI":"10.1016\/j.canlet.2024.217272","article-title":"Cellular dynamics of tumor microenvironment driving immunotherapy resistance in non-small-cell lung carcinoma","volume":"604","author":"Huang","year":"2024","journal-title":"Cancer Lett."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"117948","DOI":"10.1016\/j.bcp.2026.117948","article-title":"Inhibition of extracellular vesicle secretion by cannabidiol: A promising approach for oral squamous cell carcinoma therapy","volume":"250","author":"Feng","year":"2026","journal-title":"Biochem. Pharmacol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Liu, W., Wang, Z., Li, Z., Li, S., Shi, X., Xu, Y., and Wang, J. (2025). Lipid metabolic reprogramming in the tumor microenvironment and its mechanistic role in immunosuppressive cells. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1728354"},{"key":"ref_59","first-page":"725","article-title":"The role of lipid metabolic interactions in reshaping the tumor microenvironment","volume":"58","author":"Yang","year":"2025","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s12944-023-01807-1","article-title":"Lipid metabolism reprogramming in tumor-associated macrophages and implications for therapy","volume":"22","author":"Qiao","year":"2023","journal-title":"Lipids Health Dis."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Korbecki, J., Siminska, D., Gassowska-Dobrowolska, M., Listos, J., Gutowska, I., Chlubek, D., and Baranowska-Bosiacka, I. (2021). Chronic and Cycling Hypoxia: Drivers of Cancer Chronic Inflammation through HIF-1 and NF-kappaB Activation: A Review of the Molecular Mechanisms. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910701"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"He, Z., and Zhang, S. (2021). Tumor-Associated Macrophages and Their Functional Transformation in the Hypoxic Tumor Microenvironment. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.741305"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"54676","DOI":"10.18632\/oncotarget.10578","article-title":"Circulating exosomes potentiate tumor malignant properties in a mouse model of chronic sleep fragmentation","volume":"7","author":"Khalyfa","year":"2016","journal-title":"Oncotarget"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1016\/j.chest.2016.08.1438","article-title":"Tumor Cell Malignant Properties Are Enhanced by Circulating Exosomes in Sleep Apnea","volume":"150","author":"Almendros","year":"2016","journal-title":"Chest"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: Summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"giaa151","DOI":"10.1093\/gigascience\/giaa151","article-title":"SoupX removes ambient RNA contamination from droplet-based single-cell RNA sequencing data","volume":"9","author":"Young","year":"2020","journal-title":"Gigascience"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","article-title":"Dictionary learning for integrative, multimodal and scalable single-cell analysis","volume":"42","author":"Hao","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"979","DOI":"10.12688\/f1000research.73600.1","article-title":"Doublet identification in single-cell sequencing data using scDblFinder","volume":"10","author":"Germain","year":"2021","journal-title":"F1000Research"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s13059-021-02584-9","article-title":"Comparison and evaluation of statistical error models for scRNA-seq","volume":"23","author":"Choudhary","year":"2022","journal-title":"Genome Biol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1186\/s13059-019-1874-1","article-title":"Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression","volume":"20","author":"Hafemeister","year":"2019","journal-title":"Genome Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/s41592-019-0619-0","article-title":"Fast, sensitive and accurate integration of single-cell data with Harmony","volume":"16","author":"Korsunsky","year":"2019","journal-title":"Nat. Methods"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Cao, Y., Wang, X., and Peng, G. (2020). SCSA: A Cell Type Annotation Tool for Single-Cell RNA-seq Data. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00490"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"D870","DOI":"10.1093\/nar\/gkac947","article-title":"CellMarker 2.0: An updated database of manually curated cell markers in human\/mouse and web tools based on scRNA-seq data","volume":"51","author":"Hu","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"baz046","DOI":"10.1093\/database\/baz046","article-title":"PanglaoDB: A web server for exploration of mouse and human single-cell RNA sequencing data","volume":"2019","author":"Franzen","year":"2019","journal-title":"Database"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"ClusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS J. Integr. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Street, K., Risso, D., Fletcher, R.B., Das, D., Ngai, J., Yosef, N., Purdom, E., and Dudoit, S. (2018). Slingshot: Cell lineage and pseudotime inference for single-cell transcriptomics. BMC Genom., 19.","DOI":"10.1186\/s12864-018-4772-0"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/s41596-024-01045-4","article-title":"CellChat for systematic analysis of cell-cell communication from single-cell transcriptomics","volume":"20","author":"Jin","year":"2025","journal-title":"Nat. Protoc."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Sanz-Rubio, D., Khalyfa, A., Qiao, Z., Ullate, J., Marin, J.M., Kheirandish-Gozal, L., and Gozal, D. (2021). Cell-Selective Altered Cargo Properties of Extracellular Vesicles Following In Vitro Exposures to Intermittent Hypoxia. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115604"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nbt.1621","article-title":"Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation","volume":"28","author":"Trapnell","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1093\/bioinformatics\/btr355","article-title":"Identification of novel transcripts in annotated genomes using RNA-Seq","volume":"27","author":"Roberts","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nbt.2450","article-title":"Differential analysis of gene regulation at transcript resolution with RNA-seq","volume":"31","author":"Trapnell","year":"2013","journal-title":"Nat. Biotechnol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7819\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:26:21Z","timestamp":1788542781000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":83,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177819"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177819","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]}}}