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Molecular Cancer
Published in: Molecular Cancer 1/2020

01-12-2020 | Melanoma | Review

The complex relationship between MITF and the immune system: a Melanoma ImmunoTherapy (response) Factor?

Authors: Robert Ballotti, Yann Cheli, Corine Bertolotto

Published in: Molecular Cancer | Issue 1/2020

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Abstract

The clinical benefit of immune checkpoint inhibitory therapy (ICT) in advanced melanomas is limited by primary and acquired resistance. The molecular determinants of the resistance have been extensively studied, but these discoveries have not yet been translated into therapeutic benefits. As such, a paradigm shift in melanoma treatment, to surmount the therapeutic impasses linked to the resistance, is an important ongoing challenge.
This review outlines the multifaceted interplay between microphthalmia-associated transcription factor (MITF), a major determinant of the biology of melanoma cells, and the immune system. In melanomas, MITF functions downstream oncogenic pathways and microenvironment stimuli that restrain the immune responses. We highlight how MITF, by controlling differentiation and genome integrity, may regulate melanoma-specific antigen expression by interfering with the endolysosomal pathway, KARS1, and antigen processing and presentation. MITF also modulates the expression of coinhibitory receptors, i.e., PD-L1 and HVEM, and the production of an inflammatory secretome, which directly affects the infiltration and/or activation of the immune cells.
Furthermore, MITF is also a key determinant of melanoma cell plasticity and tumor heterogeneity, which are undoubtedly one of the major hurdles for an effective immunotherapy. Finally, we briefly discuss the role of MITF in kidney cancer, where it also plays a key role, and in immune cells, establishing MITF as a central mediator in the regulation of immune responses in melanoma and other cancers.
We propose that a better understanding of MITF and immune system intersections could help in the tailoring of current ICT in melanomas and pave the way for clinical benefits and long-lasting responses.
Literature
1.
Karimkhani C, Green AC, Nijsten T, Weinstock MA, Dellavalle RP, Naghavi M, et al. The global burden of melanoma: results from the global burden of disease study 2015. Br J Dermatol. 2017;177:134–40.PubMedPubMedCentralCrossRef
2.
Cho H, Mariotto AB, Schwartz LM, Luo J, Woloshin S. When do changes in cancer survival mean progress? The insight from population incidence and mortality. J Natl Cancer Inst. 2014;2014:187–97.CrossRef
3.
Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, et al. Mutations of the BRAF gene in human cancer. Nature. 2002;417:949–54.PubMedCrossRef
4.
Johnson DB, Menzies AM, Zimmer L, Eroglu Z, Ye F, Zhao S, et al. Acquired BRAF inhibitor resistance: a multicenter meta-analysis of the spectrum and frequencies, clinical behaviour, and phenotypic associations of resistance mechanisms. Eur J Cancer. 2015;51:2792–9.PubMedPubMedCentralCrossRef
5.
Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, et al. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371:1877–88.PubMedCrossRef
6.
Long GV, Flaherty KT, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, et al. Dabrafenib plus trametinib versus dabrafenib monotherapy in patients with metastatic BRAF V600E/ K-mutant melanoma: Long-term survival and safety analysis of a phase 3 study. Ann Oncol. 2017;28:1631–9.PubMedPubMedCentralCrossRef
7.
Brunet JF, Denizot F, Luciani MF, Roux-Dosseto M, Suzan M, Mattei MG, et al. A new member of the immunoglobulin superfamily-CTLA-4. Nature. 1988;328:267–70.CrossRef
8.
Yang JC, Rosenberg SA. Adoptive T-Cell therapy for cancer. Adv Immunol. 2016;130:279–294.
9.
Urbani F, Ferraresi V, Capone I, Macchia I, Palermo B, Nuzzo C, et al. Clinical and immunological outcomes in high-risk resected melanoma patients receiving peptide-based vaccination and interferon alpha, with or without Dacarbazine preconditioning: a phase II study. Front Oncol. 2020;10:202. https://​doi.​org/​10.​3389/​fonc.​2020.​00202.
10.
Bayan C-AY, Lopez AT, Gartrell RD, Komatsubara KM, Bogardus M, Rao N, et al. The role of Oncolytic viruses in the treatment of melanoma. Curr Oncol Rep. 2018;20:80.PubMedPubMedCentralCrossRef
11.
Hodi FS, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Cowey CL, et al. Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol. 2018;19:1480–92.PubMedCrossRef
12.
Asmar R, Yang J, Carvajal RD. Clinical utility of nivolumab in the treatment of advanced melanoma. Ther Clin Risk Manag. 2016;12:313–25.PubMedPubMedCentral
13.
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019;381:1535–46.PubMedCrossRef
14.
Koustas E, Sarantis P, Papavassiliou AG, Karamouzis MV. The resistance mechanisms of checkpoint inhibitors in solid tumors. Biomolecules. 2020;10:1–17.CrossRef
15.
16.
Goding CR, Arnheiter H. MITF — the first 25 years. Genes Dev. 2019;33:983–1007.
17.
Bertolotto C, Lesueur F, Giuliano S, Strub T, De Lichy M, Bille K, et al. A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma. Nature. 2011;480:94–8.PubMedCrossRef
18.
19.
Garraway LA, Widlund HR, Rubin MA, Getz G, Berger AJ, Ramaswamy S, et al. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature. 2005;436:117–22.PubMedCrossRef
20.
Yokoyama S, Woods SL, Boyle GM, Aoude LG, MacGregor S, Zismann V, et al. A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma. Nature. 2011;480:99–103.PubMedPubMedCentralCrossRef
21.
Hoek KS, Goding CR. Cancer stem cells versus phenotype-switching in melanoma. Pigment Cell Melanoma Res. 2010;23:746–59.PubMedCrossRef
22.
Cheli Y, Giuliano S, Botton T, Rocchi S, Hofman V, Hofman P, et al. Erratum: Mitf is the key molecular switch between mouse or human melanoma initiating cells and their differentiated progeny. Oncogene. 2011;30:2307–18.PubMedCrossRef
23.
Cheli Y, Giuliano S, Fenouille N, Allegra M, Hofman V, Hofman P, et al. Hypoxia and MITF control metastatic behaviour in mouse and human melanoma cells. Oncogene. 2012;31:2461–70.PubMedCrossRef
24.
Muller J, Krijgsman O, Tsoi J, Robert L, Hugo W, Song C, et al. Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma. Nat Commun. 2014;5:983–1007.
25.
26.
Falletta P, Sanchez-Del-Campo L, Chauhan J, Effern M, Kenyon A, Kershaw CJ, et al. Translation reprogramming is an evolutionarily conserved driver of phenotypic plasticity and therapeutic resistance in melanoma. Genes Dev. 2017;31:18–33.PubMedPubMedCentralCrossRef
27.
Vivas-García Y, Falletta P, Liebing J, Louphrasitthiphol P, Feng Y, Chauhan J, et al. Lineage-restricted regulation of SCD and fatty acid saturation by MITF controls melanoma phenotypic plasticity. Mol Cell. 2020;77:120–37.PubMedCrossRef
28.
Ohanna M, Cheli Y, Bonet C, Bonazzi VF, Allegra M, Giuliano S, et al. Secretome from senescent melanoma engages the STAT3 pathway to favor reprogramming of naive melanoma towards a tumor-initiating cell phenotype. Oncotarget. 2013;4:2212–24.PubMedPubMedCentralCrossRef
29.
Leclerc J, Garandeau D, Pandiani C, Gaudel C, Bille K, Nottet N, et al. Lysosomal acid ceramidase ASAH1 controls the transition between invasive and proliferative phenotype in melanoma cells. Oncogene. 2019;38:1282–95.PubMedCrossRef
30.
Johannessen CM, Johnson LA, Piccioni F, Townes A, Frederick DT, Donahue MK, et al. A melanocyte lineage program confers resistance to MAP kinase pathway inhibition. Nature. 2013;504:138–42.PubMedPubMedCentralCrossRef
31.
Smith MP, Ferguson J, Arozarena I, Hayward R, Marais R, Chapman A, et al. Effect of SMURF2 targeting on susceptibility to MEK inhibitors in melanoma. J Natl Cancer Inst. 2013;105:33–46.PubMedCrossRef
32.
Platanias LC. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol. 2005;5:375–86.PubMedCrossRef
33.
Shin DS, Zaretsky JM, Escuin-Ordinas H, Garcia-Diaz A, Hu-Lieskovan S, Kalbasi A, et al. Primary resistance to PD-1 blockade mediated by JAK1/2 mutations. Cancer Discov. 2017;7:188–201.PubMedCrossRef
34.
Zaretsky JM, Garcia-Diaz A, Shin DS, Escuin-Ordinas H, Hugo W, Hu-Lieskovan S, et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N Engl J Med. 2016;375:819–29.PubMedPubMedCentralCrossRef
35.
Gao J, Shi LZ, Zhao H, Chen J, Xiong L, He Q, et al. Loss of IFN-γ pathway genes in tumor cells as a mechanism of resistance to anti-CTLA-4 therapy. Cell. 2016;167:397–404.PubMedPubMedCentralCrossRef
36.
Strub T, Giuliano S, Ye T, Bonet C, Keime C, Kobi D, et al. Essential role of microphthalmia transcription factor for DNA replication, mitosis and genomic stability in melanoma. Oncogene. 2011;30:2319–32.PubMedCrossRef
37.
Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, et al. Novel MITF targets identified using a two-step DNA microarray strategy. Pigment Cell Melanoma Res. 2008;21:665–76.PubMedCrossRef
38.
Du J, Miller AJ, Widlund HR, Horstmann MA, Ramaswamy S, Fisher DE. MLANA/MART1 and SILV/PMEL17/GP100 are transcriptionally regulated by MITF in melanocytes and melanoma. Am J Pathol. 2003;163:333–43.PubMedPubMedCentralCrossRef
39.
Michaeli Y, Sinik K, Haus-Cohen M, Reiter Y. Melanoma cells present high levels of HLA-A2-tyrosinase in association with instability and aberrant intracellular processing of tyrosinase. Eur J Immunol. 2012;42:842–50.PubMedCrossRef
40.
Robila V, Ostankovitch M, Altrich-VanLith ML, Theos AC, Drover S, Marks MS, et al. MHC class II presentation of gp100 epitopes in melanoma cells requires the function of conventional endosomes and is influenced by Melanosomes. J Immunol. 2008;181:7843–52.PubMedCrossRef
41.
Orlow SJ. Melanosomes are specialized members of the lysosomal lineage of organelles. J Invest Dermatol. 1995;105:3–7.PubMedCrossRef
42.
Ploper D, Taelman VF, Robert L, Perez BS, Titz B, Chen HW, et al. MITF drives endolysosomal biogenesis and potentiates Wnt signaling in melanoma cells. Proc Natl Acad Sci U S A. 2015;112:E420–9.PubMedPubMedCentralCrossRef
43.
44.
Berger MF, Hodis E, Heffernan TP, Deribe YL, Lawrence MS, Protopopov A, et al. Melanoma genome sequencing reveals frequent PREX2 mutations. Nature. 2012;485:502–6.PubMedPubMedCentralCrossRef
45.
Krauthammer M, Kong Y, Ha BH, Evans P, Bacchiocchi A, McCusker JP, et al. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat Genet. 2012;44:1006–14.PubMedPubMedCentralCrossRef
46.
Hu-lieskovan S, Berent-maoz B, Pang J, Chmielowski B, Cherry G, Seja E, et al. Genomic and Transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell. 2017;165:35–44.
47.
Van Allen EM, Miao D, Schilling B, Shukla SA, Blank C, Zimmer L, et al. Erratum for the report “genomic correlates of response to CTLA-4 blockade in metastatic melanoma.”. Science. 2016;352:207–12.CrossRef
48.
Gubin MM, Zhang X, Schuster H, Caron E, Ward JP, Noguchi T, Ivanova Y, Hundal J, Arthur CD, Krebber WJ, Mulder GE, Toebes M, Vesely MD, Lam SSK, Korman J, Allison JP, et al. Checkpoint blockade Cancer immunotherapy targets tumour- specific mutant antigens. Nature. 2015;515:577–581. A.CrossRef
49.
Samstein RM, Lee CH, Shoushtari AN, Hellmann MD, Shen R, Janjigian YY, et al. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet. 2019;51:202–6.PubMedPubMedCentralCrossRef
50.
51.
Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2016;372:2509–20.CrossRef
52.
Germano G, Lamba S, Rospo G, Barault L, Magri A, Maione F, et al. Inactivation of DNA repair triggers neoantigen generation and impairs tumour growth. Nature. 2017;552:1–5.CrossRef
53.
Johansson PA, Stark A, Palmer JM, Bigby K, Brooks K, Rolfe O, et al. Correction to: prolonged stable disease in a uveal melanoma patient with germline MBD4 nonsense mutation treated with pembrolizumab and ipilimumab. Immunogenetics. 2019;71:433–6.PubMedCrossRef
54.
Rodrigues M, Mobuchon L, Houy A, Fiévet A, Gardrat S, Barnhill RL, et al. Outlier response to anti-PD1 in uveal melanoma reveals germline MBD4 mutations in hypermutated tumors. Nat Commun. 2018;9:1–6.CrossRef
55.
Cortellino S, Turner D, Masciullo V, Schepis F, Albino D, Daniel R, et al. The base excision repair enzyme MED1 mediates DNA damage response to antitumor drugs and is associated with mismatch repair system integrity. Proc Natl Acad Sci U S A. 2003;100:15071–6.PubMedPubMedCentralCrossRef
56.
Millar CB, Guy J, Sansom OJ, Selfridge J, MacDougall E, Hendrich B, et al. Enhanced CpG mutability and tumorigenesis in MBD4-deficient mice. Science. 2002;297:403–5.PubMedCrossRef
57.
Wong E, Yang K, Kuraguchi M, Werling U, Avdievich E, Fan K, et al. Mbd4 inactivation increases C→T transition mutations and promotes gastrointestinal tumor formation. Proc Natl Acad Sci U S A. 2002;99:14937–42.PubMedPubMedCentralCrossRef
58.
Beuret L, Ohanna M, Strub T, Allegra M, Davidson I, Bertolotto C, et al. BRCA1 is a new MITF target gene. Pigment Cell Melanoma Res. 2011;24:725–7.PubMedCrossRef
59.
Bourseguin J, Bonet C, Renaud E, Pandiani C, Boncompagni M, Giuliano S, et al. FANCD2 functions as a critical factor downstream of MiTF to maintain the proliferation and survival of melanoma cells. Sci Rep. 2016;6:36539.PubMedPubMedCentralCrossRef
60.
Giuliano S, Cheli Y, Ohanna M, Bonet C, Beuret L, Bille K, et al. Microphthalmia-associated transcription factor controls the DNA damage response and a lineage-specific senescence program in melanomas. Cancer Res. 2010;70:3813–22.PubMedCrossRef
61.
Bellacosa A, Cicchillitti L, Schepis F, Riccio A, Yeung AT, Matsumoto Y, et al. MED1, a novel human methyl-CpG-binding endonuclease, interacts with DNA mismatch repair protein MLH1. Proc Natl Acad Sci U S A. 1999;96:3969–74.PubMedPubMedCentralCrossRef
62.
Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371:2189–99.PubMedPubMedCentralCrossRef
63.
Miao D, Margolis CA, Gao W, Voss MH, Li W, Martini DJ, et al. Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. Science. 2018;806:801–6.CrossRef
64.
Wolf Y, Bartok O, Patkar S, Eli GB, Cohen S, Litchfield K, et al. UVB-induced tumor heterogeneity diminishes immune response in melanoma. Cell. 2019;179:219–35.PubMedPubMedCentralCrossRef
65.
Goodall J, Carreira S, Denat L, Kobi D, Davidson I, Nuciforo P, et al. Brn-2 represses microphthalmia-associated transcription factor expression and marks a distinct subpopulation of microphthalmia-associated transcription factor-negative melanoma cells. Cancer Res. 2008;68:7788–94.PubMedCrossRef
66.
Haq R, Shoag J, Andreu-Perez P, Yokoyama S, Edelman H, Rowe GC, et al. Oncogenic BRAF regulates oxidative metabolism via PGC1alpha and MITF. Cancer Cell. 2013;23:302–15.PubMedPubMedCentralCrossRef
67.
Ribas A, Lawrence D, Atkinson V, Agarwal S, Miller WH, Carlino MS, et al. Combined BRAF and MEK inhibition with PD-1 blockade immunotherapy in BRAF-mutant melanoma. Nat Med. 2019;25:936–40.CrossRefPubMedPubMedCentral
68.
Homet Moreno B, Mok S, Comin-Anduix B, Hu-Lieskovan S, Ribas A. Combined treatment with dabrafenib and trametinib with immune-stimulating antibodies for BRAF mutant melanoma. Oncoimmunology. 2016;5:1–8.CrossRef
69.
Zhang N, Dou Y, Liu L, Zhang X, Liu X, Zeng Q, et al. SA-49, a novel aloperine derivative, induces MITF-dependent lysosomal degradation of PD-L1. EBioMedicine. 2019;40:151–62.PubMedPubMedCentralCrossRef
70.
Papaccio F, Della Corte CM, Viscardi G, Di Liello R, Esposito G, Sparano F, et al. HGF/MET and the immune system: relevance for cancer immunotherapy. Int J Mol Sci. 2018;19:3595.PubMedCentralCrossRef
71.
Glodde N, Bald T, van den Boorn-Konijnenberg D, Nakamura K, O’Donnell JS, Szczepanski S, et al. Reactive neutrophil responses dependent on the receptor tyrosine kinase c-MET limit Cancer immunotherapy. Immunity. 2017;47:789–802.PubMedCrossRef
72.
Ferrucci PF, Gandini S, Battaglia A, Alfieri S, Di Giacomo AM, Giannarelli D, et al. Baseline neutrophil-to-lymphocyte ratio is associated with outcome of ipilimumab-treated metastatic melanoma patients. Br J Cancer. 2015;112:1904–10.PubMedPubMedCentralCrossRef
73.
Gebhardt C, Sevko A, Jiang H, Lichtenberger R, Reith M, Tarnanidis K, et al. Myeloid cells and related chronic inflammatory factors as novel predictive markers in melanoma treatment with ipilimumab. Clin Cancer Res. 2015;21:5453–9.PubMedCrossRef
74.
Shen F, Tang X, Wang Y, Yang Z, Shi X, Wang C, et al. Phenotype and expression profile analysis of Staphylococcus aureus biofilms and planktonic cells in response to licochalcone a. Appl Microbiol Biotechnol. 2015;99:359–73.PubMedCrossRef
75.
Beuret L, Flori E, Denoyelle C, Bille K, Busca R, Picardo M, et al. Up-regulation of MET expression by α-melanocyte-stimulating hormone and MITF allows hepatocyte growth factor to protect melanocytes and melanoma cells from apoptosis. J Biol Chem. 2007;282:14140–7.PubMedCrossRef
76.
McGill GG, Haq R, Nishimura EK. Fisher DE c-Met expression is regulated by Mitf in the melanocyte lineage. J Biol Chem. 2006;281:10365–73.PubMedCrossRef
77.
Aguissa-Touré AH, Li G. Genetic alterations of PTEN in human melanoma. Cell Mol Life Sci. 2012;69:1475–91.PubMedCrossRef
78.
Bucheit AD, Chen G, Siroy A, Tetzlaff M, Broaddus R, Milton D, et al. Complete loss of PTEN protein expression correlates with shorter time to brain metastasis and survival in stage IIIB/C melanoma patients with BRAFV600 mutations. Clin Cancer Res. 2014;20:5527–36.PubMedPubMedCentralCrossRef
79.
Peng W, Chen JQ, Liu C, Malu S, Creasy C, Tetzlaff MT, et al. Loss of PTEN promotes resistance to T cell-mediated immunotherapy. Cancer Discov. 2016;6:202–16.PubMedCrossRef
80.
Bonvin E, Falletta P, Shaw H, Delmas V, Goding CR. A phosphatidylinositol 3-kinase-Pax3 axis regulates Brn-2 expression in melanoma. Mol Cell Biol. 2012;32:4674–83.PubMedPubMedCentralCrossRef
81.
Pinner S, Jordan P, Sharrock K, Bazley L, Collinson L, Marais R, et al. Intravital imaging reveals transient changes in pigment production and Brn2 expression during metastatic melanoma dissemination. Cancer Res. 2009;69:7969–77.PubMedPubMedCentralCrossRef
82.
Khaled M, Larribere L, Bille K, Ortonne J-P, Ballotti R, Bertolotto C. Microphthalmia associated transcription factor is a target of the Phosphatidylinositol-3-kinase pathway. J Invest Dermatol. 2003;121:831–6.PubMedCrossRef
83.
Kim KH, Seol HJ, Kim EH, Rheey J, Jin HJ, Lee Y, et al. Wnt/β-catenin signaling is a key downstream mediator of MET signaling in glioblastoma stem cells. Neuro-Oncology. 2013;15:161–71.PubMedCrossRef
84.
Purcell R, Childs M, Maibach R, Miles C, Turner C, Zimmermann A, et al. HGF/c-met related activation of -catenin in hepatoblastoma. J Exp Clin Cancer Res. 2011;30:96.PubMedPubMedCentralCrossRef
85.
Monga SPS, Mars WM, Pediaditakis P, Bell A, Mulé K, Bowen WC, et al. Hepatocyte growth factor induces Wnt-independent nuclear translocation of β-catenin after met-β-catenin dissociation in hepatocytes. Cancer Res. 2002;62:2064–71.PubMed
86.
Spranger S, Bao R, Gajewski TF. Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity. Nature. 2015;523:231–5.PubMedCrossRef
87.
Trujillo JA, Luke JJ, Zha Y, Segal JP, Ritterhouse LL, Spranger S, et al. Secondary resistance to immunotherapy associated with β-catenin pathway activation or PTEN loss in metastatic melanoma. J Immunother Cancer. J ImmunoTher Cancer. 2019;7:1–11.CrossRef
88.
Luke JJ, Bao R, Sweis RF, Spranger S, Gajewski TF. WNT/b-catenin pathway activation correlates with immune exclusion across human cancers. Clin Cancer Res. 2019;25:3074–83.PubMedPubMedCentralCrossRef
89.
Delmas V, Beermann F, Martinozzi S, Carreira S, Ackermann J, Kumasaka M, et al. Beta-catenin induces immortalization of melanocytes by suppressing p16INK4a expression and cooperates with N-Ras in melanoma development. Genes Dev. 2007;21:2923–35.PubMedPubMedCentralCrossRef
90.
Widlund HR, Horstmann MA, Price ER, Cui J, Lessnick SL, Wu M, et al. Beta-catenin-induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor. J Cell Biol. 2002;158:1079–87.PubMedPubMedCentralCrossRef
91.
Yasumoto K, Takeda K, Saito H, Watanabe K, Takahashi K, Shibahara S. Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling. EMBO J. 2002;21:2703–14.PubMedPubMedCentralCrossRef
92.
Saito H, Yasumoto K, Takeda K, Takahashi K, Fukuzaki A, Orikasa S, et al. Melanocyte-specific microphthalmia-associated transcription factor isoform activates its own gene promoter through physical interaction with lymphoid-enhancing factor 1. J Biol Chem. 2002;277:28787–94.PubMedCrossRef
93.
Schepsky A, Bruser K, Gunnarsson GJ, Goodall J, Hallsson JH, Goding CR, et al. The microphthalmia-associated transcription factor Mitf interacts with beta-catenin to determine target gene expression. Mol Cell Biol. 2006;26:8914–27.PubMedPubMedCentralCrossRef
94.
Goodall J, Martinozzi S, Dexter TJ, Champeval D, Carreira S, Larue L, et al. Brn-2 expression controls melanoma proliferation and is directly regulated by beta-catenin. Mol Cell Biol. 2004;24:2915–22.PubMedPubMedCentralCrossRef
95.
Harris ML, Fufa TD, Palmer JW, Joshi SS, Larson DM, Incao A, et al. A direct link between MITF, innate immunity, and hair graying. PLoS Biol. 2018;16:e2003648.PubMedPubMedCentralCrossRef
96.
Praetorius C, Grill C, Stacey SN, Metcalf AM, Gorkin DU, Robinson KC, et al. A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway. Cell. 2013;155:1022–33.PubMedCrossRef
97.
Ueno N, Nishimura N, Ueno S, Endo S, Tatetsu H, Hirata S, et al. PU.1 acts as tumor suppressor for myeloma cells through direct transcriptional repression of IRF4. Oncogene. 2017;36:4481–97.PubMedCrossRef
98.
Webster DE, Barajas B, Bussat RT, Yan KJ, Neela PH, Flockhart RJ, et al. Enhancer-targeted genome editing selectively blocks innate resistance to oncokinase inhibition. Genome Res. 2014;24:751–60.PubMedPubMedCentralCrossRef
99.
Anderson AC, Joller N, Kuchroo VK. Functions in immune regulation. Immunity. 2017;44:989–1004.CrossRef
100.
Mazzarella L, Duso BA, Trapani D, Belli C, D’Amico P, Ferraro E, et al. The evolving landscape of ‘next-generation’ immune checkpoint inhibitors: a review. Eur J Cancer. 2019;117:14–31.PubMedCrossRef
101.
Derré L, Rivals JP, Jandus C, Pastor S, Rimoldi D, Romero P, et al. BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination. J Clin Invest. 2010;120:157–67.PubMedCrossRef
102.
Malissen N, Macagno N, Granjeaud S, Granier C, Moutardier V, Gaudy-Marqueste C, et al. HVEM has a broader expression than PD-L1 and constitutes a negative prognostic marker and potential treatment target for melanoma. Oncoimmunology. 2019;8:1–14.CrossRef
103.
Yu X, Zheng Y, Mao R, Su Z, Zhang J. BTLA/HVEM signaling: milestones in research and role in chronic hepatitis B virus infection. Front Immunol. 2019;10:1–8.CrossRef
104.
Landsberg J, Kohlmeyer J, Renn M, Bald T, Rogava M, Cron M, et al. Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation. Nature. 2012;490:412–6.PubMedCrossRef
105.
Soudja SM, Wehbe M, Mas A, Chasson L, De Tenbossche CP, Huijbers I, et al. Tumor-initiated inflammation overrides protective adaptive immunity in an induced melanoma model in mice. Cancer Res. 2010;70:3515–25.PubMedCrossRef
106.
Mehta A, Kim YJ, Robert L, Tsoi J, Berent-maoz B, Cochran AJ, et al. Immunotherapy resistance by inflammation-induced dedifferentiation. Cancer Discov. 2019;8:935–43.CrossRef
107.
Riesenberg S, Groetchen A, Siddaway R, Bald T, Reinhardt J, Smorra D, et al. MITF and c-Jun antagonism interconnects melanoma dedifferentiation with pro-inflammatory cytokine responsiveness and myeloid cell recruitment. Nat Commun. 2015;6:8755.PubMedCrossRef
108.
Englaro W, Bahadoran P, Bertolotto C, Buscà R, Dérijard B, Livolsi A, et al. Tumor necrosis factor alpha-mediated inhibition of melanogenesis is dependent on nuclear factor kappa B activation. Oncogene. 1999;18:1553–9.PubMedCrossRef
109.
Bertrand F, Montfort A, Marcheteau E, Imbert C, Gilhodes J, Filleron T, et al. TNFα blockade overcomes resistance to anti-PD-1 in experimental melanoma. Nat Commun. 2017;8:2256.PubMedPubMedCentralCrossRef
110.
Le Poole IC, Riker AI, Quevedo ME, Stennett LS, Wang E, Marincola FM, et al. Interferon-γ reduces melanosomal antigen expression and recognition of melanoma cells by cytotoxic T cells. Am J Pathol. 2002;160:521–8.PubMedPubMedCentralCrossRef
111.
Gollob JA, Sciambi CJ, Huang Z, Dressman HK. Gene expression changes and signaling events associated with the direct antimelanoma effect of IFN-γ. Cancer Res. 2005;65:8869–77.PubMedCrossRef
112.
Kholmanskikh O, Van Baren N, Brasseur F, Ottaviani S, Vanacker J, Arts N, et al. Interleukins 1α and 1β secreted by some melanoma cell lines strongly reduce expression of MITF-M and melanocyte differentiation antigens. Int J Cancer. 2010;127:1625–36.PubMedCrossRef
113.
Arts N, Cané S, Hennequart M, Lamy J, Bommer G, Den VEB, et al. MicroRNA-155, induced by interleukin-1β, represses the expression of microphthalmia-associated transcription factor (MITF-M) in melanoma cells. PLoS One. 2015;10:1–18.CrossRef
114.
Ohanna M, Giuliano S, Bonet C, Imbert V, Hofman V, Zangari J, et al. Senescent cells develop a PARP-1 and nuclear factor-{kappa}B-associated secretome (PNAS). Genes Dev. 2011;25:1245–61.PubMedPubMedCentralCrossRef
115.
Kamaraju AK, Bertolotto C, Chebath J, Revel M. Pax3 down-regulation and shut-off of melanogenesis in melanoma B16/F10.9 by interleukin-6 receptor signaling. J Biol Chem. 2002;277:15132–41.PubMedCrossRef
116.
Khalili JS, Liu S, Rodríguez-cruz TG, Whittington M, Liu C, Zhang M, et al. Oncogenic BRAF(V600E) promotes stromal cell-mediated immunosuppression via induction of Interleukin-1 in melanoma. Clin Cancer Res. 2013;18:5329–40.CrossRef
117.
Gide TN, Quek C, Menzies AM, Tasker AT, Shang P, Holst J, et al. Distinct immune cell populations define response to anti-PD-1 Monotherapy and anti-PD-1/anti-CTLA-4 combined therapy. Cancer Cell. 2019;35:238–55.CrossRefPubMed
118.
Pastorekova S, Gillies RJ. The role of carbonic anhydrase IX in cancer development: links to hypoxia, acidosis, and beyond. Cancer Metastasis Rev. 2019;38:65–77.PubMedPubMedCentralCrossRef
119.
Feige E, Yokoyama S, Levy C, Khaled M, Igras V, Lin RJ, et al. Hypoxia-induced transcriptional repression of the melanoma-associated oncogene MITF. Proc Natl Acad Sci U S A. 2011;108:E924–33.PubMedPubMedCentralCrossRef
120.
Guerra L, Bonetti L, Brenner D. Metabolic modulation of immunity: a new concept in Cancer immunotherapy. Cell Rep. 2020;32:107848.PubMedCrossRef
121.
Ohanna M, Cerezo M, Nottet N, Bille K, Didier R, Beranger G, et al. Pivotal role of NAMPT in the switch of melanoma cells toward an invasive and drug-resistant phenotype. Genes Dev. 2018;32:448–61.PubMedPubMedCentralCrossRef
122.
Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med. 2003;9:1269–74.PubMedCrossRef
123.
Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359:97–103.PubMedCrossRef
124.
Li Y, Tinoco R, Elmén L, Segota I, Xian Y, Fujita Y, et al. Gut microbiota dependent anti-tumor immunity restricts melanoma growth in Rnf5 −/− mice. Nat Commun. 2019;10:1492.PubMedPubMedCentralCrossRef
125.
Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, Flament C, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350:1079–84.PubMedPubMedCentralCrossRef
126.
Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350:1084–9.PubMedPubMedCentralCrossRef
127.
Durinck S, Stawiski EW, Pavía-Jiménez A, Modrusan Z, Kapur P, Jaiswal BS, et al. Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes. Nat Genet. 2015;47:13–21.PubMedCrossRef
128.
Boilève A, Carlo MI, Barthélémy P, Oudard S, Borchiellini D, Voss MH, et al. Immune checkpoint inhibitors in MITF family translocation renal cell carcinomas and genetic correlates of exceptional responders. J Immunother Cancer. 2018;6:1–10.CrossRef
129.
La Shu S, Paruchuru LB, Tay NQ, Chua YL, Yun Foo AS, Yang CM, et al. Ap4A Regulates Directional Mobility and Antigen Presentation in Dendritic Cells. iScience. 2019;16:524–34.PubMedPubMedCentralCrossRef
130.
Kitamura Y, Morii E, Jippo T, Ito A. mi-transcription factor as a regulator of mast cell differentiation. Int J Hematol. 2000;71:197–202.PubMed
131.
Morii E, Oboki K, Ishihara K, Jippo T, Hirano T, Kitamura Y. Roles of MITF for development of mast cells in mice: effects on both precursors and tissue environments. Blood. 2004;104:1656–61.PubMedCrossRef
132.
St. John AL, Abraham SN. Innate immunity and its regulation by mast cells. J Immunol. 2013;190:4458–63.PubMedCrossRef
133.
Biswas PS, Gupta S, Stirzaker RA, Kumar V, Jessberger R, Lu TT, et al. Dual regulation of IRF4 function in T and B cells is required for the coordination of T-B cell interactions and the prevention of autoimmunity. J Exp Med. 2012;209:581–96.PubMedPubMedCentralCrossRef
134.
Simonetti G, Carette A, Silva K, Wang H, De Silva NS, Heise N, et al. IRF4 controls the positioning of mature B cells in the lymphoid microenvironments by regulating NOTCH2 expression and activity. J Exp Med. 2013;210:2887–902.PubMedPubMedCentralCrossRef
135.
Lin L, Gerth AJ, Peng SL. Active inhibition of plasma cell development in resting B cells by microphthalmia-associated transcription factor. J Exp Med. 2004;200:115–22.PubMedPubMedCentralCrossRef
136.
Zhang S, Yue X, Yu J, Wang H, Liu B. MITF regulates downstream genes in response to vibrio parahaemolyticus infection in the clam meretrix petechialis. Front Immunol. 2019;10:1–12.CrossRef
137.
Sahin U, Oehm P, Derhovanessian E, Jabulowsky RA, Vormehr M, Gold M, et al. An RNA vaccine drives immunity in checkpoint-inhibitor-treated melanoma. Nature. 2020;585:107–12.PubMedCrossRef
138.
Wiedemann GM, Aithal C, Kraechan A, Heise C, Cadilha BL, Zhang J, et al. Microphthalmia-associated transcription factor (MITF) regulates immune cell migration into melanoma. Transl Oncol. 2019;12:350–60.PubMedCrossRef
139.
Yannay-Cohen N, Carmi-Levy I, Kay G, Yang CM, Han JM, Kemeny DM, et al. LysRS serves as a key signaling molecule in the immune response by regulating gene expression. Mol Cell. 2009;34:603–11.PubMedCrossRef
140.
Wahab SZ, Yang DCH. Synthesis of diadenosine-5′,5″’-P1,P4-tetraphosphate by lysyl-tRNA synthetase and a multienzyme complex of aminoacyl-tRNA synthetases from rat liver. J Biol Chem. 1985;260:5286–9.PubMed
141.
Motzik A, Amir E, Erlich T, Wang J, Kim BG, Han JM, et al. Post-translational modification of HINT1 mediates activation of MITF transcriptional activity in human melanoma cells. Oncogene. 2017;36:4732–8.
142.
Pérez-Guijarro E, Yang HH, Araya RE, El Meskini R, Michael HT, Vodnala SK, et al. Multimodel preclinical platform predicts clinical response of melanoma to immunotherapy. Nat Med. 2020;26:781–91.PubMedCrossRefPubMedCentral
143.
Hugo W, Shi H, Sun L, Piva M, Song C, Kong X, et al. Non-genomic and immune evolution of melanoma acquiring MAPKi resistance. Cell. 2015;162:1271–85.PubMedPubMedCentralCrossRef
144.
Bertolotto C, Abbe P, Hemesath TJ, Bille K, Fisher DE, Ortonne J-P, et al. Microphthalmia gene product as a signal transducer in cAMP-induced differentiation of melanocytes. J Cell Biol. 1998;142:827–35.PubMedPubMedCentralCrossRef
145.
Price ER, Horstmann MA, Wells AG, Weilbaecher KN, Takemoto CM, Landis MW, et al. Alpha-melanocyte-stimulating hormone signaling regulates expression of microphthalmia, a gene deficient in Waardenburg syndrome. J Biol Chem. 1998;273:33042–7.PubMedCrossRef
146.
Saez-Ayala M, Montenegro MF, Sanchez-Del-Campo L, Fernandez-Perez MP, Chazarra S, Freter R, et al. Directed phenotype switching as an effective antimelanoma strategy. Cancer Cell. 2013;24:105–19.PubMedCrossRef
Metadata
Title
The complex relationship between MITF and the immune system: a Melanoma ImmunoTherapy (response) Factor?
Authors
Robert Ballotti
Yann Cheli
Corine Bertolotto
Publication date
01-12-2020
Publisher
BioMed Central
Keywords
Melanoma
Melanoma
Published in
Molecular Cancer / Issue 1/2020
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/s12943-020-01290-7

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