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NMRK2 leads to the depletion of CD8+T cells by mediating the enhancement of NAD+-SIRT1-CD38 axis in PRCC-TFE3 rRCC

Oncogene (2025)Cite this article

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Abstract

PRCC-TFE3 rearrangement renal cell carcinoma (rRCC) is an independent subtype of rRCC caused by chromosomal translocation and rearrangement. Previous studies have revealed that nicotinamide riboside kinase 2 (NMRK2), which is transcriptionally upregulated by PRCC-TFE3 fusion protein, as a pivotal molecule in the energy metabolism remodeling of PRCC-TFE3 rRCC. However, the molecular mechanism by which NMRK2-mediated enhancement of nicotinamide adenine dinucleotide (NAD+) synthesis contributes to tumor progression in PRCC-TFE3 rRCC remains unclear. In this study, utilizing immune system-humanized mice model and in vitro cell models, we demonstrated that elevated expression of NMRK2 impaired the cytotoxic functions of CD8+T cells, leading to the emergence of immune-ignorant phenotypes in PRCC-TFE3 rRCC. Furthermore, it was shown that the increased NAD+ metabolism driven by NMRK2 enhanced the stability of CD38 protein through SIRT1-mediated deacetylation, which underlines impairment of CD8+T cells and the development of an immunosuppressive state in PRCC-TFE3 rRCC. Our findings not only elucidated a mechanism underlying immunological ignorance in PRCC-TFE3 rRCC but also propose potential therapeutic targets.

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Fig. 1: PRCC-TFE3 fusion protein reduced the CD8+T cells infiltration in PRCC-TFE3 rRCC independent of any deficiencies in the recruitment and proliferation of CD8+T cells.
Fig. 2: PRCC-TFE3 fusion impaired the killing function of CD8+T cells in PRCC-TFE3 rRCC.
Fig. 3: NMRK2 impaired the killing activity of CD8+T cells in PRCC-TFE3 rRCC.
Fig. 4: NMRK2 was the vital kinase that catalyzed the synthesis of NAD+ in PRCC-TFE3 rRCC.
Fig. 5: NMRK2 acted in NAD+-SIRT1-CD38 pathway and enhanced the expression level of CD38 protein.
Fig. 6: NMRK2 enhanced CD38 protein stability through SIRT1-mediated deacetylation.
Fig. 7: Deacetylated modification of CD38 protein promoted its stability by reducing the recruitment of ubiquitin molecules.
Fig. 8: Pathological and survival information of patients with PRCC-TFE3 rRCC.
Fig. 9: CD38 inhibitor enhanced the cytotoxic effect of CD8+T cells on PRCC-TFE3 rRCC cells.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

References

  1. Moch H, Amin MB, Berney DM, Comperat EM, Gill AJ, Hartmann A, et al. The 2022 World Health Organization classification of tumours of the urinary system and male genital organs-part a: renal, penile, and testicular tumours. Eur Urol. 2022;82:458–68.

    Article  PubMed  Google Scholar 

  2. Sukov WR, Hodge JC, Lohse CM, Leibovich BC, Thompson RH, Pearce KE, et al. TFE3 rearrangements in adult renal cell carcinoma: clinical and pathologic features with outcome in a large series of consecutively treated patients. Am J Surg Pathol. 2012;36:663–70.

    Article  PubMed  Google Scholar 

  3. Lin J, Tang Z, Zhang C, Dong W, Liu Y, Huang H, et al. TFE3 gene rearrangement and protein expression contribute to a poor prognosis of renal cell carcinoma. Heliyon. 2023;9:e16076.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Lee HJ, Shin DH, Kim SY, Hwang CS, Lee JH, Park WY, et al. TFE3 translocation and protein expression in renal cell carcinoma are correlated with poor prognosis. Histopathology. 2018;73:758–66.

    Article  PubMed  Google Scholar 

  5. van der Beek JN, Hol JA, Coulomb-L’Hermine A, Graf N, van Tinteren H, Pritchard-Jones K, et al. Characteristics and outcome of pediatric renal cell carcinoma patients registered in the International Society of Pediatric Oncology (SIOP) 93-01, 2001 and UK-IMPORT database: a report of the SIOP-Renal Tumor Study Group. Int J Cancer. 2021;148:2724–35.

    Article  PubMed  PubMed Central  Google Scholar 

  6. van der Beek JN, Geller JI, de Krijger RR, Graf N, Pritchard-Jones K, Drost J, et al. Characteristics and outcome of children with renal cell carcinoma: a narrative review. Cancers. 2020;12:1776.

  7. Lu Y, Zhu Y, Ma W, Liu N, Dong X, Shi Q, et al. Estrogen associates with female predominance in Xp11.2 translocation renal cell carcinoma. Sci Rep. 2023;13:6141.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zhuang W, Liu N, Guo H, Zhang C, Gan W. Gender difference analysis of Xp11.2 translocation renal cell carcinomas’s attack rate: a meta-analysis and systematic review. BMC Urol. 2020;20:130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sun G, Chen J, Liang J, Yin X, Zhang M, Yao J, et al. Integrated exome and RNA sequencing of TFE3-translocation renal cell carcinoma. Nat Commun. 2021;12:5262.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Qu Y, Wu X, Anwaier A, Feng J, Xu W, Pei X, et al. Proteogenomic characterization of MiT family translocation renal cell carcinoma. Nat Commun. 2022;13:7494.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wang B, Gan W, Han X, Li D. PRCC-TFE3 regulates migration and invasion of translocation renal cell carcinomas via activation of Drp1-dependent mitochondrial fission. Cell Biol Int. 2020;44:1727–33.

    Article  CAS  PubMed  Google Scholar 

  12. Wang B, Yin X, Gan W, Pan F, Li S, Xiang Z, et al. PRCC-TFE3 fusion-mediated PRKN/parkin-dependent mitophagy promotes cell survival and proliferation in PRCC-TFE3 translocation renal cell carcinoma. Autophagy. 2021;17:2475–93.

    Article  CAS  PubMed  Google Scholar 

  13. Sidhar SK, Clark J, Gill S, Hamoudi R, Crew AJ, Gwilliam R, et al. The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene. Hum Mol Genet. 1996;5:1333–8.

    Article  CAS  PubMed  Google Scholar 

  14. Skalsky YM, Ajuh PM, Parker C, Lamond AI, Goodwin G, Cooper CS. PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is associated with pre-mRNA splicing factors. Oncogene. 2001;20:178–87.

    Article  CAS  PubMed  Google Scholar 

  15. Yin X, Wang B, Gan W, Zhuang W, Xiang Z, Han X, et al. TFE3 fusions escape from controlling of mTOR signaling pathway and accumulate in the nucleus promoting genes expression in Xp11.2 translocation renal cell carcinomas. J Exp Clin Cancer Res. 2019;38:119.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Chen Y, Yang L, Lu Y, Liu N, Ma W, Fan H, et al. Up-regulation of NMRK2 mediated by TFE3 fusions is the key for energy metabolism adaption of Xp11.2 translocation renal cell carcinoma. Cancer Lett. 2022;538:215689.

    Article  CAS  PubMed  Google Scholar 

  17. Covarrubias AJ, Perrone R, Grozio A, Verdin E. NAD(+) metabolism and its roles in cellular processes during ageing. Nat Rev Mol Cell Biol. 2021;22:119–41.

    Article  CAS  PubMed  Google Scholar 

  18. Amjad S, Nisar S, Bhat AA, Shah AR, Frenneaux MP, Fakhro K, et al. Role of NAD(+) in regulating cellular and metabolic signaling pathways. Mol Metab. 2021;49:101195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Garten A, Schuster S, Penke M, Gorski T, de Giorgis T, Kiess W. Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nat Rev Endocrinol. 2015;11:535–46.

    Article  CAS  PubMed  Google Scholar 

  20. Jokinen R, Pirnes-Karhu S, Pietilainen KH, Pirinen E. Adipose tissue NAD(+)-homeostasis, sirtuins and poly(ADP-ribose) polymerases -important players in mitochondrial metabolism and metabolic health. Redox Biol. 2017;12:246–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Canto C, Menzies KJ, Auwerx J. NAD(+) metabolism and the control of energy homeostasis: a balancing act between mitochondria and the nucleus. Cell Metab. 2015;22:31–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Munk SHN, Merchut-Maya JM, Adelantado Rubio A, Hall A, Pappas G, Milletti G, et al. NAD(+) regulates nucleotide metabolism and genomic DNA replication. Nat Cell Biol. 2023;25:1774–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Guldenpfennig A, Hopp AK, Muskalla L, Manetsch P, Raith F, Hellweg L, et al. Absence of mitochondrial SLC25A51 enhances PARP1-dependent DNA repair by increasing nuclear NAD+ levels. Nucleic Acids Res. 2023;51:9248–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chini CCS, Zeidler JD, Kashyap S, Warner G, Chini EN. Evolving concepts in NAD(+) metabolism. Cell Metab. 2021;33:1076–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Damgaard MV, Treebak JT. What is really known about the effects of nicotinamide riboside supplementation in humans. Sci Adv. 2023;9:eadi4862.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Lv H, Lv G, Chen C, Zong Q, Jiang G, Ye D, et al. NAD(+) metabolism maintains inducible PD-L1 expression to drive tumor immune evasion. Cell Metab. 2021;33:110–27.e115.

    Article  CAS  PubMed  Google Scholar 

  27. Li M, Kirtane AR, Kiyokawa J, Nagashima H, Lopes A, Tirmizi ZA, et al. Local targeting of NAD(+) salvage pathway alters the immune tumor microenvironment and enhances checkpoint immunotherapy in glioblastoma. Cancer Res. 2021;81:1922.

    Article  PubMed  Google Scholar 

  28. Wan J, Cheng C, Hu J, Huang H, Han Q, Jie Z, et al. De novo NAD(+) synthesis contributes to CD8(+) T cell metabolic fitness and antitumor function. Cell Rep. 2023;42:113518.

    Article  CAS  PubMed  Google Scholar 

  29. Wang Y, Wang F, Wang L, Qiu S, Yao Y, Yan C, et al. NAD(+) supplement potentiates tumor-killing function by rescuing defective TUB-mediated NAMPT transcription in tumor-infiltrated T cells. Cell Rep. 2021;36:109516.

    Article  CAS  PubMed  Google Scholar 

  30. Chatterjee S, Daenthanasanmak A, Chakraborty P, Wyatt MW, Dhar P, Selvam SP, et al. CD38-NAD(+)axis regulates immunotherapeutic anti-tumor T cell response. Cell Metab. 2018;27:85–100.e108.

    Article  CAS  PubMed  Google Scholar 

  31. Rudloff MW, Zumbo P, Favret NR, Roetman JJ, Detres Roman CR, Erwin MM, et al. Hallmarks of CD8(+) T cell dysfunction are established within hours of tumor antigen encounter before cell division. Nat Immunol. 2023;24:1527–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chen L, Diao L, Yang Y, Yi X, Rodriguez BL, Li Y, et al. CD38-mediated immunosuppression as a mechanism of tumor cell escape from PD-1/PD-L1 blockade. Cancer Discov. 2018;8:1156–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Horenstein AL, Chillemi A, Zaccarello G, Bruzzone S, Quarona V, Zito A, et al. A CD38/CD203a/CD73 ectoenzymatic pathway independent of CD39 drives a novel adenosinergic loop in human T lymphocytes. Oncoimmunology. 2013;2:e26246.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Yegutkin GG, Boison D. ATP and adenosine metabolism in cancer: exploitation for therapeutic gain. Pharmacol Rev. 2022;74:797–822.

    Article  PubMed  Google Scholar 

  35. Zhang C, Wang K, Wang H. Adenosine in cancer immunotherapy: taking off on a new plane. Biochim Biophys Acta Rev Cancer. 2023;1878:189005.

    Article  CAS  PubMed  Google Scholar 

  36. Aksoy P, Escande C, White TA, Thompson M, Soares S, Benech JC, et al. Regulation of SIRT 1 mediated NAD-dependent deacetylation: a novel role for the multifunctional enzyme CD38. Biochem Biophys Res Commun. 2006;349:353–9.

    Article  CAS  PubMed  Google Scholar 

  37. Barbosa MT, Soares SM, Novak CM, Sinclair D, Levine JA, Aksoy P, et al. The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity. FASEB J. 2007;21:3629–39.

    Article  CAS  PubMed  Google Scholar 

  38. van de Donk N, Richardson PG, Malavasi F. CD38 antibodies in multiple myeloma: back to the future. Blood. 2018;131:13–29.

    Article  PubMed  Google Scholar 

  39. Green DJ, O’Steen S, Lin Y, Comstock ML, Kenoyer AL, Hamlin DK, et al. CD38-bispecific antibody pretargeted radioimmunotherapy for multiple myeloma and other B-cell malignancies. Blood. 2018;131:611–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Carretero-Iglesia L, Hall OJ, Berret J, Pais D, Estoppey C, Chimen M, et al. ISB 2001 trispecific T cell engager shows strong tumor cytotoxicity and overcomes immune escape mechanisms of multiple myeloma cells. Nat Cancer. 2024;5:1494–514.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Feng X, Zhang L, Acharya C, An G, Wen K, Qiu L, et al. Targeting CD38 suppresses induction and function of T regulatory cells to mitigate immunosuppression in multiple myeloma. Clin Cancer Res. 2017;23:4290–4300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Holmgaard RB, Zamarin D, Li Y, Gasmi B, Munn DH, Allison JP, et al. Tumor-expressed IDO recruits and activates MDSCs in a Treg-dependent manner. Cell Rep. 2015;13:412–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Favia A, Desideri M, Gambara G, D’Alessio A, Ruas M, Esposito B, et al. VEGF-induced neoangiogenesis is mediated by NAADP and two-pore channel-2-dependent Ca2+ signaling. Proc Natl Acad Sci USA. 2014;111:E4706–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Favia A, Pafumi I, Desideri M, Padula F, Montesano C, Passeri D, et al. NAADP-dependent Ca(2+) signaling controls melanoma progression, metastatic dissemination and neoangiogenesis. Sci Rep. 2016;6:18925.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Pepper C, Lin TT, Pratt G, Hewamana S, Brennan P, Hiller L, et al. Mcl-1 expression has in vitro and in vivo significance in chronic lymphocytic leukemia and is associated with other poor prognostic markers. Blood. 2008;112:3807–17.

    Article  CAS  PubMed  Google Scholar 

  46. Ludwig N, Yerneni SS, Azambuja JH, Gillespie DG, Menshikova EV, Jackson EK, et al. Tumor-derived exosomes promote angiogenesis via adenosine A(2B) receptor signaling. Angiogenesis. 2020;23:599–610.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Vijayan VV, Nair PG, Gujar S. Multiprong CD38 targeting to enhance anti-PD1 immune checkpoint blockade efficacy. Oncoimmunology. 2024;13:2400429.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Mastelic-Gavillet B, Navarro Rodrigo B, Decombaz L, Wang H, Ercolano G, Ahmed R, et al. Adenosine mediates functional and metabolic suppression of peripheral and tumor-infiltrating CD8(+) T cells. J Immunother Cancer. 2019;7:257.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Chen S, Akdemir I, Fan J, Linden J, Zhang B, Cekic C. The expression of adenosine A2b receptor on antigen-presenting cells suppresses CD8(+) T-cell responses and promotes tumor growth. Cancer Immunol Res. 2020;8:1064–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Bai Y, Zhang X, Zheng J, Liu Z, Yang Z, Zhang X. Overcoming high level adenosine-mediated immunosuppression by DZD2269, a potent and selective A2aR antagonist. J Exp Clin Cancer Res. 2022;41:302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Chan MK, Chung JY, Tang PC, Chan AS, Ho JY, Lin TP, et al. TGF-beta signaling networks in the tumor microenvironment. Cancer Lett. 2022;550:215925.

    Article  CAS  PubMed  Google Scholar 

  52. Laine A, Labiad O, Hernandez-Vargas H, This S, Sanlaville A, Leon S, et al. Regulatory T cells promote cancer immune-escape through integrin alphavbeta8-mediated TGF-beta activation. Nat Commun. 2021;12:6228.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ferrante CJ, Pinhal-Enfield G, Elson G, Cronstein BN, Hasko G, Outram S, et al. The adenosine-dependent angiogenic switch of macrophages to an M2-like phenotype is independent of interleukin-4 receptor alpha (IL-4Ralpha) signaling. Inflammation. 2013;36:921–31.

    Article  CAS  PubMed  Google Scholar 

  54. Wen ZF, Liu H, Gao R, Zhou M, Ma J, Zhang Y, et al. Tumor cell-released autophagosomes (TRAPs) promote immunosuppression through induction of M2-like macrophages with increased expression of PD-L1. J Immunother Cancer. 2018;6:151.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Park JE, Dutta B, Tse SW, Gupta N, Tan CF, Low JK, et al. Hypoxia-induced tumor exosomes promote M2-like macrophage polarization of infiltrating myeloid cells and microRNA-mediated metabolic shift. Oncogene. 2019;38:5158–73.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful to Prof. Xiaodong Han for providing necessary reagents and suggestions about experiments. UOK cell lines derived from patients were from Dr. Marston Linehan’s lab, Urologic Oncology Branch, Tumor Cell Line Repository, NCI. We would like to sincerely thank Dr. W. Marston Linehan from the National Cancer Institute in America for giving us the UOK109 and UOK120 cell lines. We thank The Translational Medicine Core Facilities, Medical School, Nanjing University, Nanjing, China, for providing the experimental equipment. We thank Dr. Dazhi Yang from AcroGenic biotechnologies for providing us with AccuraMatrix and giving us guidance in establishing 3D cell culture. We would like to thank Home for Research editorial team (www.home-for-researchers.com).

Funding

This work was supported by the National Natural Science Foundation of China (No. 82503947), the Medical Research Project of Jiangsu Province Health Commission (No. ZD2022013), the National Natural Science Foundation of China (No. 82303942), Natural Science Foundation of Jiangsu Province (No. BK20221444), and Beijing Ronghe Medical Development Foundation.

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  1. These authors contributed equally: Yi Chen, Xuwentai Liu.

Authors and Affiliations

  1. Department of Urology, Nanjing Drum Tower Hospital, State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, China

    Yi Chen, Xuwentai Liu, Xiang Dong, Fan Feng, Weidong Gan & Dongmei Li

  2. Department of Cardiology, Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

    Yi Chen

  3. Jiangsu Key Laboratory of Molecular Medicine, Division of Anatomy and Histo-embryology, Medical School, Nanjing University, Nanjing, Jiangsu, China

    Xuwentai Liu, Mengmeng Wu, Ping Dong, Weidong Ding, Luqing Zhang & Dongmei Li

  4. Department of Thoracic Surgery, Affiliated Drum Tower Hospital of Medical School of Nanjing University, Nanjing, Jiangsu, China

    Wenliang Ma

  5. Translational Medicine Core Facilities, Medical School, Nanjing University, Nanjing, Jiangsu, China

    Yibing Ding

  6. Department of Urology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China

    Ning Liu

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Contributions

YC and XWTL conceived the study, designed the experiments, and wrote the original draft. YC (same first author) also curated the data and prepared all figures. MMW verified the analytical methods, cleaned the raw data, and co-wrote the Results. XD assembled the datasets, performed the statistical analyses, and helped write the Methods section. WLM compiled the literature review and co-wrote the Introduction and Discussion. FF edited the manuscript for scientific content and revised the statistical reporting. YBD and PD polished the language and ensured compliance with journal's style. WDD checked the references and managed the response-to-reviewers documents. LQZ proofread the final text and coordinated submission logistics. DML provided the clinical samples and laboratory reagents. WDG supervised the data-collection protocol and obtained ethical approvals. NL acquired the funding, administered the project, and critically reviewed all versions of the paper. All authors read and approved the final manuscript.

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Correspondence to Ning Liu, Weidong Gan or Dongmei Li.

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Chen, Y., Liu, X., Wu, M. et al. NMRK2 leads to the depletion of CD8+T cells by mediating the enhancement of NAD+-SIRT1-CD38 axis in PRCC-TFE3 rRCC. Oncogene (2025). https://doi.org/10.1038/s41388-025-03577-9

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