{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T23:26:59Z","timestamp":1792279619158,"version":"4.4.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Children Cancer Foundation Salzburg, Austria"},{"DOI":"10.13039\/501100011852","name":"Paracelsus Medical University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100011852","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Immunol Immunother"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immune checkpoint blockade (ICB) is now part of the standard of care in the treatment of many forms of cancer, yet it lacks efficacy in some patients, necessitating adjunct therapies to support the anti-tumor immune response. Ketogenic diets (KDs), i.e., high-fat low-carbohydrate diets, have been shown to have antiproliferative and immunomodulatory effects in various preclinical cancer studies. Here, we review current knowledge of the complex interplay of KDs and the anti-tumor immune response in the context of ICB therapy, to update our understanding of diet-induced immunometabolic reprogramming in cancer. Preclinical cancer studies have revealed increased activation of and infiltration by tumor-fighting immune cells, especially CD8+\u2009T cells, but also M1 macrophages and natural killer cells, in response to a KD regimen. In contrast, immune-suppressive cells such as regulatory CD4+\u2009T lymphocytes, M2 macrophages, and myeloid-derived suppressor cells were reported to be decreased or largely unaffected in tumors of KD-fed mice. KDs also showed synergism with ICB therapy in several preclinical tumor studies. The observed effects are ascribed to the ability of KDs to improve immune cell infiltration and induce downregulation of immune-inhibitory processes, thus creating a more immunogenic tumor microenvironment. The studies reviewed herein show that altering the metabolic composition of the tumor microenvironment by a KD can boost the anti-tumor immune response and diminish even immunotherapy-resistant as well as immunologically \"cold\" tumors. However, the exact underlying mechanisms remain to be elucidated, requiring further studies before KDs can be successfully implemented as an adjunct tumor therapy to improve survival rates for cancer patients.<\/jats:p>","DOI":"10.1007\/s00262-024-03867-3","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T17:50:50Z","timestamp":1731520250000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Overcoming immunosuppression in cancer: how ketogenic diets boost immune checkpoint blockade"],"prefix":"10.1007","volume":"74","author":[{"given":"Victoria E.","family":"Stefan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela D.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Kofler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"issue":"1","key":"3867_CR1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","volume":"12","author":"D Hanahan","year":"2022","unstructured":"Hanahan D (2022) Hallmarks of cancer: new dimensions. Cancer Discov 12(1):31\u201346","journal-title":"Cancer Discov"},{"issue":"12","key":"3867_CR2","doi-asserted-by":"crossref","DOI":"10.1002\/cti2.1226","volume":"9","author":"M Wang","year":"2020","unstructured":"Wang M, Wang S, Desai J, Trapani JA, Neeson PJ (2020) Therapeutic strategies to remodel immunologically cold tumors. Clin Transl Immunology 9(12):e1226","journal-title":"Clin Transl Immunology"},{"issue":"1","key":"3867_CR3","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1186\/s13045-022-01325-0","volume":"15","author":"Y Wang","year":"2022","unstructured":"Wang Y, Zhang H, Liu C, Wang Z, Wu W, Zhang N, Zhang L, Hu J, Luo P, Zhang J, Liu Z, Peng Y, Liu Z, Tang L, Cheng Q (2022) Immune checkpoint modulators in cancer immunotherapy: recent advances and emerging concepts. J Hematol Oncol 15(1):111","journal-title":"J Hematol Oncol"},{"key":"3867_CR4","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3389\/fonc.2018.00086","volume":"8","author":"JA Seidel","year":"2018","unstructured":"Seidel JA, Otsuka A, Kabashima K (2018) Anti-PD-1 and anti-CTLA-4 therapies in cancer: mechanisms of action, efficacy, and limitations. Front Oncol 8:86","journal-title":"Front Oncol"},{"issue":"5","key":"3867_CR5","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","volume":"144","author":"D Hanahan","year":"2011","unstructured":"Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646\u2013674","journal-title":"Cell"},{"issue":"3191","key":"3867_CR6","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","volume":"123","author":"O Warburg","year":"1956","unstructured":"Warburg O (1956) On the origin of cancer cells. Science 123(3191):309\u2013314","journal-title":"Science"},{"key":"3867_CR7","doi-asserted-by":"crossref","DOI":"10.1016\/j.nut.2020.110748","volume":"74","author":"EH Mathews","year":"2020","unstructured":"Mathews EH, Visagie MH, Meyer AA, Joubert AM, Mathews GE (2020) In vitro quantification: Long-term effect of glucose deprivation on various cancer cell lines. Nutrition 74:110748","journal-title":"Nutrition"},{"issue":"10","key":"3867_CR8","doi-asserted-by":"crossref","first-page":"5230","DOI":"10.3390\/ijms22105230","volume":"22","author":"MS Williams","year":"2021","unstructured":"Williams MS, Turos E (2021) The chemistry of the ketogenic diet: updates and opportunities in organic synthesis. Int J Mol Sci 22(10):5230","journal-title":"Int J Mol Sci"},{"key":"3867_CR9","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.molmet.2019.06.026","volume":"33","author":"DD Weber","year":"2020","unstructured":"Weber DD, Aminzadeh-Gohari S, Tulipan J, Catalano L, Feichtinger RG, Kofler B (2020) Ketogenic diet in the treatment of cancer - Where do we stand? Mol Metab 33:102\u2013121","journal-title":"Mol Metab"},{"issue":"1","key":"3867_CR10","doi-asserted-by":"crossref","DOI":"10.1016\/j.bj.2023.100609","volume":"47","author":"RJ Klement","year":"2024","unstructured":"Klement RJ (2024) Anti-tumor effects of ketogenic diets and their synergism with other treatments in mice: Bayesian evidence synthesis of 1755 individual mouse survival data. Biomed J 47(1):100609","journal-title":"Biomed J"},{"key":"3867_CR11","doi-asserted-by":"crossref","first-page":"21","DOI":"10.3389\/fnut.2020.00021","volume":"7","author":"TN Seyfried","year":"2020","unstructured":"Seyfried TN, Mukherjee P, Iyikesici MS, Slocum A, Kalamian M, Spinosa JP, Chinopoulos C (2020) Consideration of ketogenic metabolic therapy as a complementary or alternative approach for managing breast cancer. Front Nutr 7:21","journal-title":"Front Nutr"},{"issue":"22","key":"3867_CR12","doi-asserted-by":"crossref","first-page":"4932","DOI":"10.3390\/nu14224932","volume":"14","author":"CY Hwang","year":"2022","unstructured":"Hwang CY, Choe W, Yoon K-S, Ha J, Kim SS, Yeo E-J, Kang I (2022) Molecular mechanisms for ketone body metabolism, signaling functions, and therapeutic potential in cancer. Nutrients 14(22):4932","journal-title":"Nutrients"},{"issue":"22","key":"3867_CR13","doi-asserted-by":"crossref","first-page":"5550","DOI":"10.3390\/cancers14225550","volume":"14","author":"P Kesarwani","year":"2022","unstructured":"Kesarwani P, Kant S, Zhao Y, Miller CR, Chinnaiyan P (2022) The influence of the ketogenic diet on the immune tolerant microenvironment in glioblastoma. Cancers 14(22):5550","journal-title":"Cancers"},{"issue":"16","key":"3867_CR14","doi-asserted-by":"crossref","first-page":"3873","DOI":"10.3390\/ijms20163873","volume":"20","author":"D Licha","year":"2019","unstructured":"Licha D, Vidali S, Aminzadeh-Gohari S, Alka O, Breitkreuz L, Kohlbacher O, Reischl RJ, Feichtinger RG, Kofler B, Huber CG (2019) Untargeted metabolomics reveals molecular effects of ketogenic diet on healthy and tumor xenograft mouse models. Int J Mol Sci 20(16):3873","journal-title":"Int J Mol Sci"},{"issue":"6","key":"3867_CR15","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0129802","volume":"10","author":"RJ Morscher","year":"2015","unstructured":"Morscher RJ, Aminzadeh-Gohari S, Feichtinger RG, Mayr JA, Lang R, Neureiter D, Sperl W, Kofler B (2015) Inhibition of neuroblastoma tumor growth by ketogenic diet and\/or calorie restriction in a CD1-Nu mouse model. PLoS ONE 10(6):e0129802","journal-title":"PLoS ONE"},{"issue":"13","key":"3867_CR16","doi-asserted-by":"crossref","first-page":"17060","DOI":"10.18632\/oncotarget.7929","volume":"7","author":"RJ Morscher","year":"2016","unstructured":"Morscher RJ, Aminzadeh-Gohari S, Hauser-Kronberger C, Feichtinger RG, Sperl W, Kofler B (2016) Combination of metronomic cyclophosphamide and dietary intervention inhibits neuroblastoma growth in a CD1-nu mouse model. Oncotarget 7(13):17060\u201317073","journal-title":"Oncotarget"},{"issue":"2","key":"3867_CR17","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1097\/WCO.0000000000000432","volume":"30","author":"D Boison","year":"2017","unstructured":"Boison D (2017) New insights into the mechanisms of the ketogenic diet. Curr Opin Neurol 30(2):187\u2013192","journal-title":"Curr Opin Neurol"},{"issue":"1","key":"3867_CR18","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12967-018-1448-0","volume":"16","author":"L Soldati","year":"2018","unstructured":"Soldati L, Di Renzo L, Jirillo E, Ascierto PA, Marincola FM, De Lorenzo A (2018) The influence of diet on anti-cancer immune responsiveness. J Transl Med 16(1):75","journal-title":"J Transl Med"},{"issue":"1","key":"3867_CR19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/immuno3010001","volume":"3","author":"S Srivastava","year":"2023","unstructured":"Srivastava S, Pawar VA, Tyagi A, Sharma KP, Kumar V, Shukla SK (2023) Immune modulatory effects of ketogenic diet in different disease conditions. Immuno 3(1):1\u201315","journal-title":"Immuno"},{"key":"3867_CR20","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1186\/s12885-016-2337-7","volume":"16","author":"DM Lussier","year":"2016","unstructured":"Lussier DM, Woolf EC, Johnson JL, Brooks KS, Blattman JN, Scheck AC (2016) Enhanced immunity in a mouse model of malignant glioma is mediated by a therapeutic ketogenic diet. BMC Cancer 16:310","journal-title":"BMC Cancer"},{"issue":"3","key":"3867_CR21","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.4049\/jimmunol.1202702","volume":"191","author":"Z Husain","year":"2013","unstructured":"Husain Z, Huang Y, Seth P, Sukhatme VP (2013) Tumor-derived lactate modifies antitumor immune response: effect on myeloid-derived suppressor cells and NK cells. J Immunol 191(3):1486\u20131495","journal-title":"J Immunol"},{"issue":"8","key":"3867_CR22","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1158\/0008-5472.CAN-21-2778","volume":"82","author":"R Wei","year":"2022","unstructured":"Wei R, Zhou Y, Li C, Rychahou P, Zhang S, Titlow WB, Bauman G, Wu Y, Liu J, Wang C, Weiss HL, Evers BM, Wang Q (2022) Ketogenesis attenuates KLF5-dependent production of CXCL12 to overcome the immunosuppressive Tumor microenvironment in colorectal cancer. Cancer Res 82(8):1575\u20131588","journal-title":"Cancer Res"},{"issue":"40","key":"3867_CR23","doi-asserted-by":"crossref","first-page":"11182","DOI":"10.1021\/acs.jafc.0c04041","volume":"68","author":"N Zhang","year":"2020","unstructured":"Zhang N, Liu C, Jin L, Zhang R, Wang T, Wang Q, Chen J, Yang F, Siebert HC, Zheng X (2020) Ketogenic diet elicits antitumor properties through inducing oxidative stress, inhibiting MMP-9 expression, and rebalancing M1\/M2 Tumor-associated macrophage phenotype in a mouse model of colon cancer. J Agric Food Chem 68(40):11182\u201311196","journal-title":"J Agric Food Chem"},{"key":"3867_CR24","volume":"92","author":"W Sun","year":"2022","unstructured":"Sun W, Yang J, Liu B, Liu Q, Wang T, Wang Q, Liu M, Li L, Wang Z, Li S, Siebert H-C, Zhang N (2022) Ketogenic diet inhibits Tumor growth by enhancing immune response, attenuating immunosuppression, inhibiting angiogenesis and EMT in CT26 colon Tumor allografts mouse model. J Funct Foods 92:105067","journal-title":"J Funct Foods"},{"issue":"11","key":"3867_CR25","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1016\/j.molcel.2021.03.037","volume":"81","author":"X Dai","year":"2021","unstructured":"Dai X, Bu X, Gao Y, Guo J, Hu J, Jiang C, Zhang Z, Xu K, Duan J, He S, Zhang J, Wan L, Liu T, Zhou X, Hung MC, Freeman GJ, Wei W (2021) Energy status dictates PD-L1 protein abundance and anti-Tumor immunity to enable checkpoint blockade. Mol Cell 81(11):2317-2331.e2316","journal-title":"Mol Cell"},{"key":"3867_CR26","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.657293","volume":"12","author":"J Traba","year":"2021","unstructured":"Traba J, Sack MN, Waldmann TA, Anton OM (2021) Immunometabolism at the nexus of cancer therapeutic efficacy and resistance. Front Immunol 12:657293","journal-title":"Front Immunol"},{"issue":"7","key":"3867_CR27","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.3390\/cancers12071757","volume":"12","author":"E Cuy\u00e0s","year":"2020","unstructured":"Cuy\u00e0s E, Verdura S, Martin-Castillo B, Alarc\u00f3n T, Lupu R, Bosch-Barrera J, Menendez JA (2020) Tumor cell-intrinsic immunometabolism and precision nutrition in cancer immunotherapy. Cancers 12(7):1757","journal-title":"Cancers"},{"issue":"9","key":"3867_CR28","doi-asserted-by":"crossref","first-page":"2021","DOI":"10.1016\/j.immuni.2023.07.002","volume":"56","author":"KM Luda","year":"2023","unstructured":"Luda KM, Longo J, Kitchen-Goosen SM, Duimstra LR, Ma EH, Watson MJ, Oswald BM, Fu Z, Madaj Z, Kupai A, Dickson BM, DeCamp LM, Dahabieh MS, Compton SE, Teis R, Kaymak I, Lau KH, Kelly DP, Puchalska P, Williams KS, Krawczyk CM, L\u00e9vesque D, Boisvert FM, Sheldon RD, Rothbart SB, Crawford PA, Jones RG (2023) Ketolysis drives CD8(+) T cell effector function through effects on histone acetylation. Immunity 56(9):2021-2035.e2028","journal-title":"Immunity"},{"issue":"8","key":"3867_CR29","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.202114323","volume":"13","author":"S Hirschberger","year":"2021","unstructured":"Hirschberger S, Strau\u00df G, Effinger D, Marstaller X, Ferstl A, M\u00fcller MB, Wu T, H\u00fcbner M, Rahmel T, Mascolo H, Exner N, He\u00df J, Kreth FW, Unger K, Kreth S (2021) Very-low-carbohydrate diet enhances human T-cell immunity through immunometabolic reprogramming. EMBO Mol Med 13(8):e14323","journal-title":"EMBO Mol Med"},{"issue":"6","key":"3867_CR30","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1080\/01635581.2013.804579","volume":"65","author":"U Schroeder","year":"2013","unstructured":"Schroeder U, Himpe B, Pries R, Vonthein R, Nitsch S, Wollenberg B (2013) Decline of lactate in tumor tissue after ketogenic diet: in vivo microdialysis study in patients with head and neck cancer. Nutr Cancer 65(6):843\u2013849","journal-title":"Nutr Cancer"},{"issue":"9","key":"3867_CR31","doi-asserted-by":"crossref","first-page":"3812","DOI":"10.1182\/blood-2006-07-035972","volume":"109","author":"K Fischer","year":"2007","unstructured":"Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M, Gottfried E, Schwarz S, Rothe G, Hoves S, Renner K, Timischl B, Mackensen A, Kunz-Schughart L, Andreesen R, Krause SW, Kreutz M (2007) Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood 109(9):3812\u20133819","journal-title":"Blood"},{"key":"3867_CR32","doi-asserted-by":"crossref","first-page":"2084195","DOI":"10.1155\/2019\/2084195","volume":"2019","author":"RG Feichtinger","year":"2019","unstructured":"Feichtinger RG, Lang R (2019) Targeting L-lactate metabolism to overcome resistance to immune therapy of melanoma and other Tumor entities. J Oncol 2019:2084195","journal-title":"J Oncol"},{"issue":"2","key":"3867_CR33","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.145207","volume":"6","author":"G Ferrere","year":"2021","unstructured":"Ferrere G, Tidjani Alou M, Liu P, Goubet AG, Fidelle M, Kepp O, Durand S, Iebba V, Fluckiger A, Daill\u00e8re R, Thelemaque C, Grajeda-Iglesias C, Alves Costa Silva C, Aprahamian F, Lefevre D, Zhao L, Ryffel B, Colomba E, Arnedos M, Drubay D, Rauber C, Raoult D, Asnicar F, Spector T, Segata N, Derosa L, Kroemer G, Zitvogel L (2021) Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade. JCI Insight 6(2):e145207","journal-title":"JCI Insight"},{"issue":"2","key":"3867_CR34","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.medj.2021.12.008","volume":"3","author":"L Yang","year":"2022","unstructured":"Yang L, TeSlaa T, Ng S, Nofal M, Wang L, Lan T, Zeng X, Cowan A, McBride M, Lu W, Davidson S, Liang G, Oh TG, Downes M, Evans R, Von Hoff D, Guo JY, Han H, Rabinowitz JD (2022) Ketogenic diet and chemotherapy combine to disrupt pancreatic cancer metabolism and growth. Med 3(2):119\u2013136","journal-title":"Med"},{"issue":"1","key":"3867_CR35","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12943-023-01714-0","volume":"22","author":"M Iglesias-Escudero","year":"2023","unstructured":"Iglesias-Escudero M, Arias-Gonz\u00e1lez N, Mart\u00ednez-C\u00e1ceres E (2023) Regulatory cells and the effect of cancer immunotherapy. Mol Cancer 22(1):26","journal-title":"Mol Cancer"},{"issue":"6","key":"3867_CR36","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/j.celrep.2019.01.041","volume":"26","author":"G Monaco","year":"2019","unstructured":"Monaco G, Lee B, Xu W, Mustafah S, Hwang YY, Carr\u00e9 C, Burdin N, Visan L, Ceccarelli M, Poidinger M, Zippelius A, Pedro de Magalh\u00e3es J, Larbi A (2019) RNA-Seq signatures normalized by mRNA abundance allow absolute deconvolution of human immune cell types. Cell Rep 26(6):1627-1640.e1627","journal-title":"Cell Rep"},{"issue":"7851","key":"3867_CR37","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/s41586-020-03045-2","volume":"591","author":"MJ Watson","year":"2021","unstructured":"Watson MJ, Vignali PDA, Mullett SJ, Overacre-Delgoffe AE, Peralta RM, Grebinoski S, Menk AV, Rittenhouse NL, DePeaux K, Whetstone RD, Vignali DAA, Hand TW, Poholek AC, Morrison BM, Rothstein JD, Wendell SG, Delgoffe GM (2021) Metabolic support of tumour-infiltrating regulatory T cells by lactic acid. Nature 591(7851):645\u2013651","journal-title":"Nature"},{"issue":"12","key":"3867_CR38","doi-asserted-by":"crossref","first-page":"110986","DOI":"10.1016\/j.celrep.2022.110986","volume":"39","author":"J Gu","year":"2022","unstructured":"Gu J, Zhou J, Chen Q, Xu X, Gao J, Li X, Shao Q, Zhou B, Zhou H, Wei S, Wang Q, Liang Y, Lu L (2022) Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-\u03b2 signaling in regulatory T cells. Cell Rep 39(12):110986","journal-title":"Cell Rep"},{"key":"3867_CR39","doi-asserted-by":"crossref","first-page":"173090","DOI":"10.1016\/j.ejphar.2020.173090","volume":"877","author":"C Yunna","year":"2020","unstructured":"Yunna C, Mengru H, Lei W, Weidong C (2020) Macrophage M1\/M2 polarization. Eur J Pharmacol 877:173090","journal-title":"Eur J Pharmacol"},{"issue":"1","key":"3867_CR40","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s12929-019-0568-z","volume":"26","author":"Y Chen","year":"2019","unstructured":"Chen Y, Song Y, Du W, Gong L, Chang H, Zou Z (2019) Tumor-associated macrophages: an accomplice in solid tumor progression. J Biomed Sci 26(1):78","journal-title":"J Biomed Sci"},{"key":"3867_CR41","doi-asserted-by":"crossref","first-page":"1157291","DOI":"10.3389\/fimmu.2023.1157291","volume":"14","author":"L Xiao","year":"2023","unstructured":"Xiao L, Wang Q, Peng H (2023) Tumor-associated macrophages: new insights on their metabolic regulation and their influence in cancer immunotherapy. Front Immunol 14:1157291","journal-title":"Front Immunol"},{"issue":"2","key":"3867_CR42","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.cmet.2018.10.015","volume":"29","author":"P Puchalska","year":"2019","unstructured":"Puchalska P, Martin SE, Huang X, Lengfeld JE, Daniel B, Graham MJ, Han X, Nagy L, Patti GJ, Crawford PA (2019) Hepatocyte-macrophage acetoacetate shuttle protects against tissue fibrosis. Cell Metab 29(2):383-398.e387","journal-title":"Cell Metab"},{"issue":"1","key":"3867_CR43","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1186\/s12916-022-02352-x","volume":"20","author":"C Huang","year":"2022","unstructured":"Huang C, Wang J, Liu H, Huang R, Yan X, Song M, Tan G, Zhi F (2022) Ketone body \u03b2-hydroxybutyrate ameliorates colitis by promoting M2 macrophage polarization through the STAT6-dependent signaling pathway. BMC Med 20(1):148","journal-title":"BMC Med"},{"issue":"4","key":"3867_CR44","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1080\/15384101.2018.1444305","volume":"17","author":"X Mu","year":"2018","unstructured":"Mu X, Shi W, Xu Y, Xu C, Zhao T, Geng B, Yang J, Pan J, Hu S, Zhang C, Zhang J, Wang C, Shen J, Che Y, Liu Z, Lv Y, Wen H, You Q (2018) Tumor-derived lactate induces M2 macrophage polarization via the activation of the ERK\/STAT3 signaling pathway in breast cancer. Cell Cycle 17(4):428\u2013438","journal-title":"Cell Cycle"},{"issue":"1","key":"3867_CR45","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3390\/microorganisms12010230","volume":"12","author":"A Vojdani","year":"2024","unstructured":"Vojdani A, Koksoy S, Vojdani E, Engelman M, Benzvi C, Lerner A (2024) Natural killer cells and cytotoxic T cells: complementary partners against microorganisms and cancer. Microorganisms 12(1):230","journal-title":"Microorganisms"},{"issue":"2","key":"3867_CR46","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.cmet.2018.07.008","volume":"28","author":"B Isaacson","year":"2018","unstructured":"Isaacson B, Mandelboim O (2018) Sweet killers: NK cells need glycolysis to kill Tumors. Cell Metab 28(2):183\u2013184","journal-title":"Cell Metab"},{"key":"3867_CR47","doi-asserted-by":"crossref","first-page":"622896","DOI":"10.3389\/fonc.2021.622896","volume":"11","author":"FAI Ehlers","year":"2021","unstructured":"Ehlers FAI, Mahaweni NM, Olieslagers TI, Bos GMJ, Wieten L (2021) Activated natural killer cells withstand the relatively low glucose concentrations found in the bone marrow of multiple myeloma patients. Front Oncol. 11:622896","journal-title":"Front Oncol"},{"issue":"11","key":"3867_CR48","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2319254121","volume":"121","author":"S Sheppard","year":"2024","unstructured":"Sheppard S, Srpan K, Lin W, Lee M, Delconte RB, Owyong M, Carmeliet P, Davis DM, Xavier JB, Hsu KC, Sun JC (2024) Fatty acid oxidation fuels natural killer cell responses against infection and cancer. Proc Natl Acad Sci U S A 121(11):e2319254121","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"3867_CR49","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s40164-024-00505-7","volume":"13","author":"J Lu","year":"2024","unstructured":"Lu J, Luo Y, Rao D, Wang T, Lei Z, Chen X, Zhang B, Li Y, Liu B, Xia L, Huang W (2024) Myeloid-derived suppressor cells in cancer: therapeutic targets to overcome tumor immune evasion. Exp Hematol Oncol 13(1):39","journal-title":"Exp Hematol Oncol"},{"key":"3867_CR50","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.747863","author":"J Li","year":"2021","unstructured":"Li J, Bolyard C, Xin G, Li Z (2021) Targeting metabolic pathways of myeloid cells improves cancer immunotherapy. Front Cell Dev Biol. 9:747863","journal-title":"Front Cell Dev Biol"},{"key":"3867_CR51","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.3389\/fimmu.2019.01399","volume":"10","author":"D Yan","year":"2019","unstructured":"Yan D, Adeshakin AO, Xu M, Afolabi LO, Zhang G, Chen YH, Wan X (2019) Lipid metabolic pathways confer the immunosuppressive function of myeloid-derived suppressor cells in Tumor. Front Immunol 10:1399","journal-title":"Front Immunol"},{"issue":"5","key":"3867_CR52","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.trecan.2023.01.007","volume":"9","author":"L Arpinati","year":"2023","unstructured":"Arpinati L, Scherz-Shouval R (2023) From gatekeepers to providers: regulation of immune functions by cancer-associated fibroblasts. Trends Cancer 9(5):421\u2013443","journal-title":"Trends Cancer"},{"key":"3867_CR53","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev-pathol-042020-042741","volume":"16","author":"S Bagchi","year":"2021","unstructured":"Bagchi S, Yuan R, Engleman EG (2021) Immune checkpoint inhibitors for the treatment of cancer: clinical impact and mechanisms of response and resistance. Annu Rev Pathol 16:223\u2013249","journal-title":"Annu Rev Pathol"},{"issue":"12","key":"3867_CR54","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/s41577-021-00541-y","volume":"21","author":"K DePeaux","year":"2021","unstructured":"DePeaux K, Delgoffe GM (2021) Metabolic barriers to cancer immunotherapy. Nat Rev Immunol 21(12):785\u2013797","journal-title":"Nat Rev Immunol"},{"issue":"10","key":"3867_CR55","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1158\/0008-5472.CAN-23-2742","volume":"84","author":"S Murphy","year":"2024","unstructured":"Murphy S, Rahmy S, Gan D, Liu G, Zhu Y, Manyak M, Duong L, He J, Schofield JH, Schafer ZT, Li J, Lu X, Lu X (2024) Ketogenic diet alters the epigenetic and immune landscape of prostate cancer to overcome resistance to immune checkpoint blockade therapy. Cancer Res 84(10):1597\u20131612","journal-title":"Cancer Res"},{"issue":"1","key":"3867_CR56","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/nm0116-8","volume":"22","author":"K Weintraub","year":"2016","unstructured":"Weintraub K (2016) Take two: combining immunotherapy with epigenetic drugs to tackle cancer. Nat Med 22(1):8\u201310","journal-title":"Nat Med"},{"issue":"9","key":"3867_CR57","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.3390\/biom11091373","volume":"11","author":"S Chen","year":"2021","unstructured":"Chen S, Zhou X, Yang X, Li W, Li S, Hu Z, Ling C, Shi R, Liu J, Chen G, Song N, Jiang X, Sui X, Gao Y (2021) Dual blockade of lactate\/GPR81 and PD-1\/PD-L1 pathways enhances the anti-Tumor effects of metformin. Biomolecules 11(9):1373","journal-title":"Biomolecules"},{"issue":"1","key":"3867_CR58","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1158\/2159-8290.CD-21-0030","volume":"12","author":"C Vernieri","year":"2022","unstructured":"Vernieri C, Fuc\u00e0 G, Ligorio F, Huber V, Vingiani A, Iannelli F, Raimondi A, Rinchai D, Frig\u00e8 G, Belfiore A, Lalli L, Chiodoni C, Cancila V, Zanardi F, Ajazi A, Cortellino S, Vallacchi V, Squarcina P, Cova A, Pesce S, Frati P, Mall R, Corsetto PA, Rizzo AM, Ferraris C, Folli S, Garassino MC, Capri G, Bianchi G, Colombo MP, Minucci S, Foiani M, Longo VD, Apolone G, Torri V, Pruneri G, Bedognetti D, Rivoltini L, de Braud F (2022) Fasting-mimicking diet is safe and reshapes metabolism and antitumor immunity in patients with cancer. Cancer Discov 12(1):90\u2013107","journal-title":"Cancer Discov"},{"key":"3867_CR59","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1016\/j.ejca.2022.05.046","volume":"172","author":"F Ligorio","year":"2022","unstructured":"Ligorio F, Fuc\u00e0 G, Provenzano L, Lobefaro R, Zanenga L, Vingiani A, Belfiore A, Lorenzoni A, Alessi A, Pruneri G, de Braud F, Vernieri C (2022) Exceptional tumour responses to fasting-mimicking diet combined with standard anticancer therapies: a sub-analysis of the NCT03340935 trial. Eur J Cancer 172:300\u2013310","journal-title":"Eur J Cancer"},{"issue":"3","key":"3867_CR60","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.trecan.2022.12.006","volume":"9","author":"O Bla\u017eevit\u0161","year":"2023","unstructured":"Bla\u017eevit\u0161 O, Di Tano M, Longo VD (2023) Fasting and fasting mimicking diets in cancer prevention and therapy. Trends Cancer 9(3):212\u2013222","journal-title":"Trends Cancer"}],"container-title":["Cancer Immunology, Immunotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-024-03867-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00262-024-03867-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00262-024-03867-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T12:48:44Z","timestamp":1738241324000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00262-024-03867-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,13]]},"references-count":60,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1]]}},"alternative-id":["3867"],"URL":"https:\/\/doi.org\/10.1007\/s00262-024-03867-3","relation":{},"ISSN":["1432-0851"],"issn-type":[{"value":"1432-0851","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,13]]},"assertion":[{"value":"10 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 November 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"RL declares relevant financial activities (travel support from Bristol-Myers Squibb, Sanofi-Aventis; research grant from Bristol-Myers Squibb (institution)). VES, DDW, and BK declare no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"23"}}