Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

MAIT cell plasticity generates CD4+ MAIT cells that promote HCC progression via metabolic crosstalk with tumor cells

Cellular & Molecular Immunology (2026)Cite this article

Subjects

Abstract

Mucosal-associated invariant T cells (MAITs) are enriched in the liver and closely related to human hepatocellular carcinoma (HCC), but their role is controversial. Whether and how the plasticity of MAITs modulates HCC progression remain to be explored. Here, we revealed that CD4+ MAITs displaying Th17 features were the major source of IL-17A in human HCC. IL-17A from Th17-polarized CD4+ MAITs promoted HCC progression by enhancing lipid storage and tumor cell proliferation in a PPARĪ± dependent manner. Additionally, we showed that both TCR-dependent and TCR-independent activation signaling induced Th17-polarized CD4+ MAIT differentiation and that strong signaling promoted their differentiation. Moreover, IL-17A production in CD4+ MAITs was promoted by glycolysis via posttranscriptional regulation, and tumor cell-derived kynurenine enhanced glycolysis and IL-17A production through the AHR pathway. These findings demonstrate that the plasticity of MAITs and the generation of CD4+ MAITs promote HCC progression via metabolic crosstalk with tumor cells.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: CD4+ MAITs are the major source of IL-17A in human HCC tumors.
Fig. 2: CD4+ Th17-polarized MAITs are differentiated from CD8+ MAITs.
Fig. 3: IL-17A facilitates the proliferation of tumor cells by enhancing PPARĪ±-mediated lipid storage.
Fig. 4: CD4+ Th17-polarized MAITs are positively correlated with tumor progression in HCC patients.
Fig. 5: CD4+ Th17-polarized MAITs contribute to tumor progression.
Fig. 6: Kyn from tumor cells promotes glycolysis and IL-17A production in CD4+ Th17-polarized MAITs by activating AHR.
Fig. 7

Data availability

All raw sequencing reads for single-cell RNA-seq data (PRJNA1175005), bulk RNA-seq data (PRJNA1013717), and CUT&Tag-seq data (PRJNA1018210) have been deposited in the National Center for Biotechnology Information Sequence Read Archive. Source data are provided with this paper.

References

  1. Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, et al. Hepatocellular carcinoma. Nat Rev Dis Prim. 2021;7:6 https://doi.org/10.1038/s41572-020-00240-3.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  2. Sperandio RC, Pestana RC, Miyamura BV, Kaseb AO. Hepatocellular carcinoma immunotherapy. Annu Rev Med. 2022;73:267ā€“78. https://doi.org/10.1146/annurev-med-042220-021121.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  3. Llovet JM, Castet F, Heikenwalder M, Maini MK, Mazzaferro V, Pinato DJ, et al. Immunotherapies for hepatocellular carcinoma. Nat Rev Clin Oncol. 2022;19:151ā€“72. https://doi.org/10.1038/s41571-021-00573-2.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  4. Provine NM, Klenerman P. MAIT cells in health and disease. Annu Rev Immunol. 2020;38:203ā€“28. https://doi.org/10.1146/annurev-immunol-080719-015428.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  5. Kjer-Nielsen L, Patel O, Corbett AJ, Le Nours J, Meehan B, Liu L, et al. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature. 2012;491:717ā€“23. https://doi.org/10.1038/nature11605.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  6. Godfrey DI, Koay HF, McCluskey J, Gherardin NA. The biology and functional importance of MAIT cells. Nat Immunol. 2019;20:1110ā€“28. https://doi.org/10.1038/s41590-019-0444-8.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  7. Toubal A, Nel I, Lotersztajn S, Lehuen A. Mucosal-associated invariant T cells and disease. Nat Rev Immunol. 2019;19:643ā€“57. https://doi.org/10.1038/s41577-019-0191-y.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  8. Duan M, Goswami S, Shi JY, Wu LJ, Wang XY, Ma JQ, et al. Activated and exhausted MAIT cells foster disease progression and indicate poor outcome in hepatocellular carcinoma. Clin Cancer Res Off J Am Assoc Cancer Res. 2019;25:3304ā€“16. https://doi.org/10.1158/1078-0432.CCR-18-3040.

    ArticleĀ  Google ScholarĀ 

  9. Zheng C, Zheng L, Yoo JK, Guo H, Zhang Y, Guo X, et al. Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing. Cell. 2017;169:1342ā€“56 e1316. https://doi.org/10.1016/j.cell.2017.05.035.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  10. Tao H, Pan Y, Chu S, Li L, Xie J, Wang P, et al. Differential controls of MAIT cell effector polarization by mTORC1/mTORC2 via integrating cytokine and costimulatory signals. Nat Commun. 2021;12:2029. https://doi.org/10.1038/s41467-021-22162-8.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  11. Garner LC, Amini A, FitzPatrick M, Lett MJ, Hess GF, Filipowicz Sinnreich M, et al. Single-cell analysis of human MAIT cell transcriptional, functional and clonal diversity. Nat Immunol. 2023;24:1565ā€“78. https://doi.org/10.1038/s41590-023-01575-1.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  12. Magalhaes I, Pingris K, Poitou C, Bessoles S, Venteclef N, Kiaf B, et al. Mucosal-associated invariant T cell alterations in obese and type 2 diabetic patients. J Clin Investig. 2015;125:1752ā€“62. https://doi.org/10.1172/JCI78941.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  13. Carolan E, Tobin LM, Mangan BA, Corrigan M, Gaoatswe G, Byrne G, et al. Altered distribution and increased IL-17 production by mucosal-associated invariant T cells in adult and childhood obesity. J Immunol. 2015;194:5775ā€“80. https://doi.org/10.4049/jimmunol.1402945.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  14. Toubal A, Kiaf B, Beaudoin L, Cagninacci L, Rhimi M, Fruchet B, et al. Mucosal-associated invariant T cells promote inflammation and intestinal dysbiosis leading to metabolic dysfunction during obesity. Nat Commun. 2020;11:3755. https://doi.org/10.1038/s41467-020-17307-0.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  15. Willing A, Jager J, Reinhardt S, Kursawe N, Friese MA. Production of IL-17 by MAIT cells is increased in multiple sclerosis and is associated with IL-7 receptor expression. J Immunol. 2018;200:974ā€“82. https://doi.org/10.4049/jimmunol.1701213.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  16. Zhang LW, et al. Expression of interleukin-17 in primary Sjogrenā€™s syndrome and the correlation with disease severity: A systematic review and meta-analysis. Scand J Immunol. 2018;87:e12649. https://doi.org/10.1111/sji.12649.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  17. Rha MS, Yoon YH, Koh JY, Jung JH, Lee HS, Park SK, et al. IL-17A-producing sinonasal MAIT cells in patients with chronic rhinosinusitis with nasal polyps. J Allergy Clin Immunol. 2022;149:599ā€“609.e597. https://doi.org/10.1016/j.jaci.2021.07.037.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  18. Lu B, Liu M, Wang J, Fan H, Yang D, Zhang L, et al. IL-17 production by tissue-resident MAIT cells is locally induced in children with pneumonia. Mucosal Immunol. 2020;13:824ā€“35. https://doi.org/10.1038/s41385-020-0273-y.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  19. Li X, Fu S, Cheng H, Ma M, Song Z, Li J, et al. Differentiation of type 17 mucosal-associated invariant T cells in circulation contributes to the severity of sepsis. Am J Pathol. 2024;194:1248ā€“61. https://doi.org/10.1016/j.ajpath.2024.03.010.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  20. Fu S, Liu M, Zhu C, Zhang H, Zhao C, Xie Y, et al. Regulatory MAIT cells controlled by beta1 adrenergic receptor signaling contribute to hepatocellular carcinoma progression. Hepatology. 2023;78:72ā€“87. https://doi.org/10.1097/HEP.0000000000000014.

    ArticleĀ  PubMedĀ  Google ScholarĀ 

  21. Arner EN, Rathmell JC. Metabolic programming and immune suppression in the tumor microenvironment. Cancer cell. 2023;41:421ā€“33. https://doi.org/10.1016/j.ccell.2023.01.009.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  22. DePeaux K, Delgoffe GM. Metabolic barriers to cancer immunotherapy. Nat Rev Immunol. 2021;21:785ā€“97. https://doi.org/10.1038/s41577-021-00541-y.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  23. Oā€™Sullivan D, Sanin DE, Pearce EJ, Pearce EL. Metabolic interventions in the immune response to cancer. Nat Rev Immunol. 2019;19:324ā€“35. https://doi.org/10.1038/s41577-019-0140-9.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  24. Kao KC, Vilbois S, Tsai CH, Ho PC. Metabolic communication in the tumour-immune microenvironment. Nat Cell Biol. 2022;24:1574ā€“83. https://doi.org/10.1038/s41556-022-01002-x.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  25. Roy DG, Kaymak I, Williams KS, Ma EH, Jones RG. Immunometabolism in the tumor microenvironment. Annu Rev Cancer Biol. 2021;5:137ā€“59.

    ArticleĀ  Google ScholarĀ 

  26. Dias J, Boulouis C, Gorin JB, van den Biggelaar R, Lal KG, Gibbs A, et al. The CD4(-)CD8(-) MAIT cell subpopulation is a functionally distinct subset developmentally related to the main CD8(+) MAIT cell pool. Proc Natl Acad Sci USA. 2018;115:E11513ā€“E22. https://doi.org/10.1073/pnas.1812273115.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  27. Martin-Perez M, Urdiroz-Urricelqui U, Bigas C, Benitah SA. The role of lipids in cancer progression and metastasis. Cell Metab. 2022;34:1675ā€“99. https://doi.org/10.1016/j.cmet.2022.09.023.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  28. Bai D-S, Zhang C, Chen P, Jin S-J, Jiang G-Q. The prognostic correlation of AFP level at diagnosis with pathological grade, progression, and survival of patients with hepatocellular carcinoma. Sci Rep. 2017;7:12870. https://doi.org/10.1038/s41598-017-12834-1.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  29. Yoshikawa M, Morine Y, Ikemoto T, Imura S, Higashijima J, Iwahashi S, et al. Elevated preoperative serum CEA level is associated with poor prognosis in patients with hepatocellular carcinoma through the epithelialā€“mesenchymal transition. Anticancer Res. 2017;37:1169ā€“76. https://doi.org/10.21873/anticanres.11430.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  30. Zhang W, Wang Y, Dong X, Yang B, Zhou H, Chen L, et al. Elevated serum CA19-9 indicates severe liver inflammation and worse survival after curative resection in hepatitis B-related hepatocellular carcinoma. Biosci Trends. 2021;15:397ā€“405. https://doi.org/10.5582/bst.2021.01517.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  31. Ruf B, Bruhns M, Babaei S, Kedei N, Ma L, Revsine M, et al. Tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin. Cell. 2023;186:3686ā€“705.e3632. https://doi.org/10.1016/j.cell.2023.07.026.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  32. Lafita-Navarro MC, Perez-Castro L, Zacharias LG, Barnes S, DeBerardinis RJ, Conacci-Sorrell M. The transcription factors aryl hydrocarbon receptor and MYC cooperate in the regulation of cellular metabolism. J Biol Chem. 2020;295:12398ā€“407. https://doi.org/10.1074/jbc.AC120.014189.

    ArticleĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  33. Mascanfroni ID, Takenaka MC, Yeste A, Patel B, Wu Y, Kenison JE, et al. Metabolic control of type 1 regulatory T cell differentiation by AHR and HIF1-Ī±. Nat Med. 2015;21:638ā€“46. https://doi.org/10.1038/nm.3868.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  34. Opitz CA, Litzenburger UM, Sahm F, Ott M, Tritschler I, Trump S, et al. An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature. 2011;478:197ā€“203. https://doi.org/10.1038/nature10491.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  35. Liu Y, Liang X, Dong W, Fang Y, Lv J, Zhang T, et al. Tumor-repopulating cells induce PD-1 expression in CD8(+) T cells by transferring kynurenine and AhR Activation. Cancer cell. 2018;33:480ā€“94.e487. https://doi.org/10.1016/j.ccell.2018.02.005.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  36. Wegener M, Dietz KJ. The mutual interaction of glycolytic enzymes and RNA in post-transcriptional regulation. RNA. 2022;28:1446ā€“68. https://doi.org/10.1261/rna.079210.122.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  37. Chang CH, Curtis JD, Maggi LB Jr, Faubert B, Villarino AV, O'Sullivan D, et al. Posttranscriptional control of T cell effector function by aerobic glycolysis. Cell. 2013;153:1239ā€“51. https://doi.org/10.1016/j.cell.2013.05.016.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  38. Castello A, Hentze MW, Preiss T. Metabolic Enzymes Enjoying New Partnerships as RNA-Binding Proteins. Trends Endocrinol Metab: TEM. 2015;26:746ā€“57. https://doi.org/10.1016/j.tem.2015.09.012.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  39. De Rosa V, Galgani M, Porcellini A, Colamatteo A, Santopaolo M, Zuchegna C, et al. Glycolysis controls the induction of human regulatory T cells by modulating the expression of FOXP3 exon 2 splicing variants. Nat Immunol. 2015;16:1174ā€“84. https://doi.org/10.1038/ni.3269.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  40. Millet P, Vachharajani V, McPhail L, Yoza B, McCall CE. GAPDH Binding to TNF-alpha mRNA contributes to posttranscriptional repression in monocytes: a novel mechanism of communication between inflammation and metabolism. J Immunol. 2016;196:2541ā€“51. https://doi.org/10.4049/jimmunol.1501345.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  41. Zhao J, Chen X, Herjan T, Li X. The role of interleukin-17 in tumor development and progression. J Exp Med. 2020;217 https://doi.org/10.1084/jem.20190297.

  42. Ma S, Cheng Q, Cai Y, Gong H, Wu Y, Yu X, et al. IL-17A produced by gammadelta T cells promotes tumor growth in hepatocellular carcinoma. Cancer Res. 2014;74:1969ā€“82. https://doi.org/10.1158/0008-5472.CAN-13-2534.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  43. Gallagher C, Mahon JM, O'Neill C, Cassidy FC, Dunbar H, De Barra C, et al. Mucosal-associated invariant T cells are altered in patients with Hidradenitis Suppurativa and contribute to the inflammatory milieu. J Investig Dermatol. 2023;143:1094ā€“97.e1092. https://doi.org/10.1016/j.jid.2022.11.011.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  44. Priya R, Brutkiewicz RR. MR1 tetramer-based artificial APCs expand MAIT cells from human peripheral blood that effectively kill glioblastoma cells. Immunohorizons. 2021;5:500ā€“11. https://doi.org/10.4049/immunohorizons.2100003.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  45. Labuz D, Cacioppo J, Li K, AubĆ© J, Leung DT. Enhancing mucosal-associated invariant T cell function and expansion with human selective serum. ImmunoHorizons. 2023;7:116ā€“24. https://doi.org/10.4049/immunohorizons.2200082.

    ArticleĀ  CASĀ  PubMedĀ  PubMed CentralĀ  Google ScholarĀ 

  46. Kedia-Mehta N, Pisarska MM, Rollings C, O'Neill C, De Barra C, Foley C, et al. The proliferation of human mucosal-associated invariant T cells requires a MYC-SLC7A5-glycolysis metabolic axis. Sci Signal. 2023;16:eabo2709 https://doi.org/10.1126/scisignal.abo2709.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  47. O'brien A, Loftus RM, Pisarska MM, Tobin LM, Bergin R, Wood N, et al. Obesity reduces mTORC1 activity in mucosal-associated invariant T cells, driving defective metabolic and functional responses. J Immunol. 2019;202:3404ā€“11. https://doi.org/10.4049/jimmunol.1801600.

    ArticleĀ  CASĀ  PubMedĀ  Google ScholarĀ 

  48. Vitiello GA, Miller G. Targeting the interleukin-17 immune axis for cancer immunotherapy. J Exp Med. 2020;217 https://doi.org/10.1084/jem.20190456.

Download references

Acknowledgements

We thank the NIH Tetramer Core Facility for providing the hMR1-5-OP-RU tetramer and hMR1-6-FP tetramer. We thank Professor Zeming Zhang for helping us provide the scRNA-seq data. This work was supported by the National Natural Science Foundation of China (32325020, 92254304, and 82372778), the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB0940202), the CAS Project for Young Scientists in Basic Research (YSBR-074), the Key Science & Technology Project of Anhui Province (202523n10050009), and the Fundamental Research Funds for the Central Universities (WK9100250109).

Author information

Authors and Affiliations

  1. Department of Health Management Center of the First Affiliated Hospital, State Key Laboratory of Immune Response and Immunotherapy, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China

    Sicheng Fu,Ā Changfeng Zhao,Ā Miya Su,Ā Jun Pan,Ā Yuwei Zhang,Ā Xiaohu Wang,Ā Wenhao Jia,Ā Xinmin Chu,Ā Shi Chen,Ā Tengchuan Jin,Ā Zhigang Tian,Ā Huimin ZhangĀ &Ā Li Bai

  2. Department of Immunology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China

    Maoyu Tang

  3. Insitute of Health and Medicine, Hefei Comprehensive National Science Center, Hefei, China

    Maoyu Tang,Ā Yusheng ChenĀ &Ā Li Bai

  4. Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China

    Sanwei ChenĀ &Ā Yeben Qian

  5. Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China

    Lijian Chen

  6. Department of Medical Oncology, Division of Life Sciences and Medicine, The First Affiliated Hospital of University of Science and Technology of China, Hefei, China

    Yubei Sun

  7. Department of Hepatobiliary Surgery, State Key Laboratory of Immune Response and Immunotherapy, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China

    Lianxin Liu

  8. Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China

    Hua Wang

  9. Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, China

    Li Bai

Authors
  1. Sicheng Fu
    View author publications

    Search author on:PubMedĀ Google Scholar

  2. Maoyu Tang
    View author publications

    Search author on:PubMedĀ Google Scholar

  3. Changfeng Zhao
    View author publications

    Search author on:PubMedĀ Google Scholar

  4. Sanwei Chen
    View author publications

    Search author on:PubMedĀ Google Scholar

  5. Miya Su
    View author publications

    Search author on:PubMedĀ Google Scholar

  6. Jun Pan
    View author publications

    Search author on:PubMedĀ Google Scholar

  7. Yuwei Zhang
    View author publications

    Search author on:PubMedĀ Google Scholar

  8. Xiaohu Wang
    View author publications

    Search author on:PubMedĀ Google Scholar

  9. Wenhao Jia
    View author publications

    Search author on:PubMedĀ Google Scholar

  10. Xinmin Chu
    View author publications

    Search author on:PubMedĀ Google Scholar

  11. Shi Chen
    View author publications

    Search author on:PubMedĀ Google Scholar

  12. Yusheng Chen
    View author publications

    Search author on:PubMedĀ Google Scholar

  13. Lijian Chen
    View author publications

    Search author on:PubMedĀ Google Scholar

  14. Tengchuan Jin
    View author publications

    Search author on:PubMedĀ Google Scholar

  15. Zhigang Tian
    View author publications

    Search author on:PubMedĀ Google Scholar

  16. Yubei Sun
    View author publications

    Search author on:PubMedĀ Google Scholar

  17. Yeben Qian
    View author publications

    Search author on:PubMedĀ Google Scholar

  18. Lianxin Liu
    View author publications

    Search author on:PubMedĀ Google Scholar

  19. Hua Wang
    View author publications

    Search author on:PubMedĀ Google Scholar

  20. Huimin Zhang
    View author publications

    Search author on:PubMedĀ Google Scholar

  21. Li Bai
    View author publications

    Search author on:PubMedĀ Google Scholar

Contributions

S.C.F. and L.B. conceived the idea and wrote the manuscript. S.C.F., Y.B.Q., L.X.L., H.W., H.M.Z., and L.B. designed the experiments and discussed the results. S.C.F., M.Y.T., C.F.Z., M.Y.S., J.P., Y.W.Z., X.H.W., W.H.J., and S.C. performed the experiments, S.W.C., X.M.C., Y.S.C., L.J.C., T.C.J., Z.G.T, Y.B.S., Y.B.Q., L.X.L. and H.W. provided materials.

Corresponding authors

Correspondence to Sicheng Fu, Yeben Qian, Lianxin Liu, Hua Wang, Huimin Zhang or Li Bai.

Ethics declarations

Competing interests

The authors declare that they have no competing interests. Z.G.T. is the Co-Editor-in-Chief of Cellular & Molecular Immunology, and L.B. is an editorial board member of Cellular & Molecular Immunology, but they have not been involved in the peer review or the decision-making of the article.

Additional information

Publisherā€™s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fu, S., Tang, M., Zhao, C. et al. MAIT cell plasticity generates CD4+ MAIT cells that promote HCC progression via metabolic crosstalk with tumor cells. Cell Mol Immunol (2026). https://doi.org/10.1038/s41423-026-01409-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Version of record:

  • DOI: https://doi.org/10.1038/s41423-026-01409-8

Keywords

Search

Advanced search

Quick links