Emerging Roles of MITF As a Crucial Regulator of Immunity

Overview

Journal Exp Mol Med

Specialties Biochemistry
Molecular Biology

Date 2024 Feb 13

PMID 38351314

Authors

Aram Lee

Jihyun Lim

Jong-Seok Lim

Affiliations

Soon will be listed here.

Abstract

Microphthalmia-associated transcription factor (MITF), a basic helix-loop-helix leucine zipper transcription factor (bHLH-Zip), has been identified as a melanocyte-specific transcription factor and plays a critical role in melanocyte survival, differentiation, function, proliferation and pigmentation. Although numerous studies have explained the roles of MITF in melanocytes and in melanoma development, the function of MITF in the hematopoietic or immune system-beyond its function in melanin-producing cells-is not yet fully understood. However, there is convincing and increasing evidence suggesting that MITF may play multiple important roles in immune-related cells. Therefore, this review is focused on recent advances in elucidating novel functions of MITF in cancer progression and immune responses to cancer. In particular, we highlight the role of MITF as a central modulator in the regulation of immune responses, as elucidated in recent studies.

Citing Articles

Melanin deposition and key molecular features in Xenopus tropicalis oocytes.

Yi H, Liang W, Yang S, Liu H, Deng J, Han S BMC Biol. 2025; 23(1):62.

PMID: 40016733 PMC: 11866844. DOI: 10.1186/s12915-025-02168-0.

Microbes, macrophages, and melanin: a unifying theory of disease as exemplified by cancer.

Berg S, Berg J Front Immunol. 2025; 15:1493978.

PMID: 39981299 PMC: 11840190. DOI: 10.3389/fimmu.2024.1493978.

Modified human skin cell isolation protocol and its influence on keratinocyte and melanocyte culture.

Liu Z, Jin S, Cheng D, Chen H, Wang Y, Ji C Regen Ther. 2024; 26:203-212.

PMID: 38948130 PMC: 11214264. DOI: 10.1016/j.reth.2024.05.014.

References

Liu J, Fisher D . Lighting a path to pigmentation: mechanisms of MITF induction by UV. Pigment Cell Melanoma Res. 2010; 23(6):741-5. DOI: 10.1111/j.1755-148X.2010.00775.x. View

Yasumoto K, Yokoyama K, Shibata K, Tomita Y, Shibahara S . Microphthalmia-associated transcription factor as a regulator for melanocyte-specific transcription of the human tyrosinase gene. Mol Cell Biol. 1994; 14(12):8058-70. PMC: 359344. DOI: 10.1128/mcb.14.12.8058-8070.1994. View

Guo Y, Olle L, Proano-Perez E, Aparicio C, Guerrero M, Munoz-Cano R . MRGPRX2 signaling involves the Lysyl-tRNA synthetase and MITF pathway. Front Immunol. 2023; 14:1154108. PMC: 10206166. DOI: 10.3389/fimmu.2023.1154108. View

Carreras J, Kikuti Y, Hiraiwa S, Miyaoka M, Tomita S, Ikoma H . High PTX3 expression is associated with a poor prognosis in diffuse large B-cell lymphoma. Cancer Sci. 2021; 113(1):334-348. PMC: 8748251. DOI: 10.1111/cas.15179. View

Garza N, Swaminathan A, Maremanda K, Zulkifli M, Gohil V . Mitochondrial copper in human genetic disorders. Trends Endocrinol Metab. 2022; 34(1):21-33. PMC: 9780195. DOI: 10.1016/j.tem.2022.11.001. View

Hu Frisk J, Kjellen L, Kaler S, Pejler G, Ohrvik H . Copper Regulates Maturation and Expression of an MITF:Tryptase Axis in Mast Cells. J Immunol. 2017; 199(12):4132-4141. PMC: 5728160. DOI: 10.4049/jimmunol.1700786. View

Wiedemann G, Aithal C, Kraechan A, Heise C, Cadilha B, Zhang J . Microphthalmia-Associated Transcription Factor (MITF) Regulates Immune Cell Migration into Melanoma. Transl Oncol. 2018; 12(2):350-360. PMC: 6290759. DOI: 10.1016/j.tranon.2018.10.014. View

Cabrita R, Mitra S, Sanna A, Ekedahl H, Lovgren K, Olsson H . The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy Response. Cancers (Basel). 2020; 12(3). PMC: 7140048. DOI: 10.3390/cancers12030742. View

Sanchez-Del-Campo L, Marti-Diaz R, Montenegro M, Gonzalez-Guerrero R, Hernandez-Caselles T, Martinez-Barba E . MITF induces escape from innate immunity in melanoma. J Exp Clin Cancer Res. 2021; 40(1):117. PMC: 8015040. DOI: 10.1186/s13046-021-01916-8. View

10.

Cheli Y, Tulic M, El Hachem N, Nottet N, Jacquel A, Gesson M . ITGBL1 is a new immunomodulator that favors development of melanoma tumors by inhibiting natural killer cells cytotoxicity. Mol Cancer. 2021; 20(1):12. PMC: 7789764. DOI: 10.1186/s12943-020-01306-2. View

11.

Ballotti R, Cheli Y, Bertolotto C . The complex relationship between MITF and the immune system: a Melanoma ImmunoTherapy (response) Factor?. Mol Cancer. 2020; 19(1):170. PMC: 7718690. DOI: 10.1186/s12943-020-01290-7. View

12.

Haymaker C, Wu R, Ritthipichai K, Bernatchez C, Forget M, Chen J . BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties. Oncoimmunology. 2015; 4(8):e1014246. PMC: 4570103. DOI: 10.1080/2162402X.2015.1014246. View

13.

Vucinic D, Grahovac M, Grahovac B, Mohar Vitezic B, Kovac L, Belusic-Gobic M . PD-L1 expression is regulated by microphthalmia-associated transcription factor (MITF) in nodular melanoma. Pathol Res Pract. 2021; 229:153725. DOI: 10.1016/j.prp.2021.153725. View

14.

Wang H, Zhang H, Chen Y, Wang H, Tian Y, Yi X . Targeting Wnt/β-Catenin Signaling Exacerbates Ferroptosis and Increases the Efficacy of Melanoma Immunotherapy via the Regulation of MITF. Cells. 2022; 11(22). PMC: 9688625. DOI: 10.3390/cells11223580. View

15.

Sloane R, White M, Witt R, Banerjee A, Davies M, Han G . Identification of MicroRNA-mRNA Networks in Melanoma and Their Association with PD-1 Checkpoint Blockade Outcomes. Cancers (Basel). 2021; 13(21). PMC: 8582574. DOI: 10.3390/cancers13215301. View

16.

Kenski J, Huang X, Vredevoogd D, de Bruijn B, Traets J, Ibanez-Molero S . An adverse tumor-protective effect of IDO1 inhibition. Cell Rep Med. 2023; 4(2):100941. PMC: 9975322. DOI: 10.1016/j.xcrm.2023.100941. View

17.

Bersanelli M, Rebuzzi S, Roviello G, Catalano M, Brunelli M, Rizzo M . Immune checkpoint inhibitors in non-conventional histologies of renal-cell carcinoma. Hum Vaccin Immunother. 2023; 19(1):2171672. PMC: 10012923. DOI: 10.1080/21645515.2023.2171672. View

18.

Mansky K, Sankar U, Han J, Ostrowski M . Microphthalmia transcription factor is a target of the p38 MAPK pathway in response to receptor activator of NF-kappa B ligand signaling. J Biol Chem. 2002; 277(13):11077-83. DOI: 10.1074/jbc.M111696200. View

19.

Oppezzo A, Rosselli F . The underestimated role of the microphthalmia-associated transcription factor (MiTF) in normal and pathological haematopoiesis. Cell Biosci. 2021; 11(1):18. PMC: 7805242. DOI: 10.1186/s13578-021-00529-0. View

20.

Luchin A, Purdom G, Murphy K, Clark M, Angel N, Cassady A . The microphthalmia transcription factor regulates expression of the tartrate-resistant acid phosphatase gene during terminal differentiation of osteoclasts. J Bone Miner Res. 2000; 15(3):451-60. DOI: 10.1359/jbmr.2000.15.3.451. View