S-adenosylmethionine blocks tumorigenesis and with immune checkpoint inhibitor enhances anti-cancer efficacy against BRAF mutant and wildtype melanomas.
Anti-PD-1 antibody
B16
Immune checkpoint inhibitors
MITF
Melanin
Melanoma
Phenotype switching
S-adenosylmethionine
YUMMER1.7
Journal
Neoplasia (New York, N.Y.)
ISSN: 1476-5586
Titre abrégé: Neoplasia
Pays: United States
ID NLM: 100886622
Informations de publication
Date de publication:
Feb 2023
Feb 2023
Historique:
received:
01
11
2022
revised:
27
12
2022
accepted:
28
12
2022
pubmed:
14
1
2023
medline:
25
1
2023
entrez:
13
1
2023
Statut:
ppublish
Résumé
Despite marked success in treatment with immune checkpoint inhibitor (CPI), only a third of patients are responsive. Thus, melanoma still has one of the highest prevalence and mortality rates; which has led to a search for novel combination therapies that might complement CPI. Aberrant methylomes are one of the mechanisms of resistance to CPI therapy. S-adenosylmethionine (SAM), methyl donor of important epigenetic processes, has significant anti-cancer effects in several malignancies; however, SAM's effect has never been extensively investigated in melanoma. We demonstrate that SAM modulates phenotype switching of melanoma cells and directs the cells towards differentiation indicated by increased melanogenesis (melanin and melanosome synthesis), melanocyte-like morphology, elevated Mitf and Mitf activators' expression, increased antigen expression, reduced proliferation, and reduced stemness genes' expression. Consistently, providing SAM orally, reduced tumor growth and progression, and metastasis of syngeneic BRAF mutant and wild-type (WT) melanoma mouse models. Of note, SAM and anti-PD-1 antibody combination treatment had enhanced anti-cancer efficacy compared to monotherapies, showed significant reduction in tumor growth and progression, and increased survival. Furthermore, SAM and anti-PD-1 antibody combination triggered significantly higher immune cell infiltration, higher CD8
Identifiants
pubmed: 36638586
pii: S1476-5586(22)00099-9
doi: 10.1016/j.neo.2022.100874
pmc: PMC9840362
pii:
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
S-Adenosylmethionine
7LP2MPO46S
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
100874Informations de copyright
Copyright © 2022. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
Cancer Res. 2000 May 15;60(10):2703-9
pubmed: 10825144
Database (Oxford). 2015 Sep 30;2015:
pubmed: 26424083
J Immunol. 1987 Jul 1;139(1):202-6
pubmed: 3295052
Cancer Res. 2008 Feb 1;68(3):650-6
pubmed: 18245463
Lancet. 2018 Sep 15;392(10151):971-984
pubmed: 30238891
Nat Biotechnol. 2020 Jun;38(6):675-678
pubmed: 32444850
Nat Commun. 2020 Jun 5;11(1):2858
pubmed: 32504051
Cell Rep. 2014 May 22;7(4):989-98
pubmed: 24794441
J Cell Biol. 1998 Aug 10;142(3):827-35
pubmed: 9700169
Int J Mol Med. 2018 Feb;41(2):1055-1061
pubmed: 29207034
J Immunol. 2002 Jul 15;169(2):642-6
pubmed: 12097364
J Clin Invest. 2021 Apr 15;131(8):
pubmed: 33690225
Exp Dermatol. 2014 Nov;23(11):813-8
pubmed: 25180917
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Nat Rev Immunol. 2020 Jan;20(1):25-39
pubmed: 31570880
Arch Biochem Biophys. 2014 Dec 1;563:28-34
pubmed: 25111671
Cancers (Basel). 2022 Dec 22;15(1):
pubmed: 36612044
Cancer Res. 2019 Nov 15;79(22):5769-5784
pubmed: 31582381
Oncoimmunology. 2015 Aug 12;5(1):e1067745
pubmed: 26942087
J Surg Res. 1998 Feb 15;75(1):49-53
pubmed: 9614856
Front Oncol. 2020 Aug 07;10:1152
pubmed: 32850327
Cell Death Dis. 2017 Jun 1;8(6):e2836
pubmed: 28569770
Nature. 2012 Oct 18;490(7420):412-6
pubmed: 23051752
Cancer Cell. 2013 Jul 8;24(1):105-19
pubmed: 23792190
Am J Clin Nutr. 2002 Nov;76(5):1151S-7S
pubmed: 12418493
Pigment Cell Res. 2006 Aug;19(4):290-302
pubmed: 16827748
Genome Biol. 2014;15(12):550
pubmed: 25516281
Elife. 2021 Jan 13;10:
pubmed: 33438577
Pharmacotherapy. 2004 Nov;24(11):1501-7
pubmed: 15537554
Ther Clin Risk Manag. 2016 Feb 26;12:313-25
pubmed: 27013881
Mol Cancer. 2020 Dec 5;19(1):170
pubmed: 33276788
J Invest Dermatol. 2015 Feb;135(2):352-358
pubmed: 25142731
Trends Mol Med. 2006 Sep;12(9):406-14
pubmed: 16899407
J Dermatol Sci. 2013 Jul;71(1):45-57
pubmed: 23726358
Science. 1996 Nov 22;274(5291):1363-6
pubmed: 8910274
Blood. 2009 Jul 16;114(3):535-46
pubmed: 19451549
J Immunol. 2005 Mar 15;174(6):3416-20
pubmed: 15749875
J Nutr Biochem. 2008 Jun;19(6):384-91
pubmed: 17869084
Cancer Manag Res. 2019 Sep 19;11:8529-8538
pubmed: 31572007
Front Oncol. 2020 Sep 02;10:1361
pubmed: 32983966
Biomark Res. 2020 Sep 29;8:49
pubmed: 33005420
Cell Rep. 2016 Aug 30;16(9):2348-58
pubmed: 27545889
Eur J Immunol. 1999 Jan;29(1):45-53
pubmed: 9933085
Adv Exp Med Biol. 2019;1164:179-196
pubmed: 31576549
J Biol Chem. 1997 Jun 20;272(25):16040-7
pubmed: 9188509
Bone Res. 2020 Jul 22;8:28
pubmed: 32714613
Cancer Discov. 2018 Aug;8(8):935-943
pubmed: 29899062
Cell. 2015 Jun 18;161(7):1681-96
pubmed: 26091043
Int J Oncol. 2011 Aug;39(2):401-8
pubmed: 21567086
J Invest Dermatol. 2014 Feb;134(2):441-451
pubmed: 23934065
Cancer Res. 2010 Jul 1;70(13):5213-9
pubmed: 20551059
Int J Cancer. 2001 Sep 1;93(5):617-22
pubmed: 11477569
Biochem J. 1996 Nov 1;319 ( Pt 3):929-33
pubmed: 8921001
Nat Genet. 2003 Jul;34(3):267-73
pubmed: 12808457
Lab Invest. 2007 Nov;87(11):1077-91
pubmed: 17724448
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Nat Commun. 2019 Sep 19;10(1):4278
pubmed: 31537801
J Oncol. 2019 Apr 28;2019:5269062
pubmed: 31182961
Genes Dev. 2006 Dec 15;20(24):3426-39
pubmed: 17182868
Nat Chem Biol. 2013 May;9(5):300-6
pubmed: 23455543
Nat Med. 1996 May;2(5):574-7
pubmed: 8616718
J Pathol. 2014 May;233(1):39-50
pubmed: 24399611
Cancers (Basel). 2016 Mar 11;8(3):
pubmed: 26978405
Mol Immunol. 2017 Jul;87:227-239
pubmed: 28511092
N Engl J Med. 2017 Dec 21;377(25):2500-2501
pubmed: 29262275
Nature. 2020 Sep;585(7824):277-282
pubmed: 32879489
Pigment Cell Melanoma Res. 2008 Dec;21(6):665-76
pubmed: 19067971
Cell. 2018 Aug 9;174(4):843-855.e19
pubmed: 30017245
Oncogene. 2004 May 20;23(23):4130-5
pubmed: 15007389
Cancer Res. 1992 Jun 15;52(12):3361-6
pubmed: 1596894
Oncogene. 2012 May 10;31(19):2461-70
pubmed: 21996743
Eur J Immunol. 2019 Oct;49(10):1457-1973
pubmed: 31633216
Cancers (Basel). 2021 Feb 01;13(3):
pubmed: 33535484
Immunity. 2009 Nov 20;31(5):787-98
pubmed: 19879162
Curr Protoc Immunol. 2001 May;Chapter 20:Unit 20.1
pubmed: 18432774
Nat Rev Cancer. 2012 Mar 22;12(4):252-64
pubmed: 22437870
Nature. 2013 Aug 22;500(7463):415-21
pubmed: 23945592
Sci Rep. 2019 Jan 28;9(1):780
pubmed: 30692593
Nature. 2005 Jul 7;436(7047):117-22
pubmed: 16001072
Cancer Med. 2015 May;4(5):732-44
pubmed: 25619880
Cell Prolif. 2018 Aug;51(4):e12441
pubmed: 29484738
Int J Mol Sci. 2016 Jul 15;17(7):
pubmed: 27428965
Postepy Dermatol Alergol. 2013 Feb;30(1):30-41
pubmed: 24278043
Oncotarget. 2017 Dec 26;9(4):5169-5183
pubmed: 29435170
J Immunol. 1999 Nov 1;163(9):4826-32
pubmed: 10528183
Physiol Rev. 2019 Jan 1;99(1):115-160
pubmed: 30354964
Mol Med Rep. 2015 Mar;11(3):1566-72
pubmed: 25384676
Cell Rep. 2022 Mar 29;38(13):110582
pubmed: 35354055
Transl Oncol. 2020 Mar;13(3):100738
pubmed: 32114384
Genes Dev. 2019 Oct 1;33(19-20):1295-1318
pubmed: 31575676
Clin Cancer Res. 2015 Feb 15;21(4):687-92
pubmed: 25501578
Cancer Discov. 2021 Mar;11(3):599-613
pubmed: 33334730
J Invest Dermatol. 2010 Jul;130(7):1877-86
pubmed: 20376064
Oncogene. 2011 May 19;30(20):2307-18
pubmed: 21278797
Crit Rev Oncol Hematol. 2017 Jul;115:36-49
pubmed: 28602168
Transl Oncol. 2019 Feb;12(2):350-360
pubmed: 30502589
Obes Rev. 2011 May;12(5):e21-31
pubmed: 20576005
J Surg Res. 1995 Jul;59(1):66-74
pubmed: 7630139
Sci Rep. 2019 Jun 26;9(1):9280
pubmed: 31243305