Tissue-resident memory T cells from a metastatic vaginal melanoma patient are tumor-responsive T cells and increase after anti-PD-1 treatment.
CD8-Positive T-Lymphocytes
Immune Evation
Immunotherapy
Melanoma
Journal
Journal for immunotherapy of cancer
ISSN: 2051-1426
Titre abrégé: J Immunother Cancer
Pays: England
ID NLM: 101620585
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
accepted:
05
04
2022
entrez:
13
5
2022
pubmed:
14
5
2022
medline:
18
5
2022
Statut:
ppublish
Résumé
Vaginal melanoma (VM) is a rare cancer and has a poor response to immune checkpoint blockade (ICB). CD8 Using longitudinal samples, we explored the evolution of VM mutations by whole-exome sequencing and RNAseq, we also defined the immune context using multiplex immunohistochemistry and nanostring pan cancer immune profile. Then using fresh single cell suspensions of the metastatic samples, we explored VM T cells via mass cytometry and single cell RNAseq and T cell receptor sequencing (TCRseq). Finally, we investigated TRM, pre-TRM and exhausted T cell function against melanoma neo-antigens and melanoma differentiation antigens in vitro. Primary VM was non-inflamed and devoid of CD8 In this study, we identified TRM clusters in VM metastases from a patient, but not primary disease. We showed TRM location at the tumor margin, and their superior functional response to autologous tumor cells, predicted neoantigens and melanoma differentiation antigens. These CD8
Sections du résumé
BACKGROUND
Vaginal melanoma (VM) is a rare cancer and has a poor response to immune checkpoint blockade (ICB). CD8
METHODS
Using longitudinal samples, we explored the evolution of VM mutations by whole-exome sequencing and RNAseq, we also defined the immune context using multiplex immunohistochemistry and nanostring pan cancer immune profile. Then using fresh single cell suspensions of the metastatic samples, we explored VM T cells via mass cytometry and single cell RNAseq and T cell receptor sequencing (TCRseq). Finally, we investigated TRM, pre-TRM and exhausted T cell function against melanoma neo-antigens and melanoma differentiation antigens in vitro.
RESULTS
Primary VM was non-inflamed and devoid of CD8
CONCLUSIONS
In this study, we identified TRM clusters in VM metastases from a patient, but not primary disease. We showed TRM location at the tumor margin, and their superior functional response to autologous tumor cells, predicted neoantigens and melanoma differentiation antigens. These CD8
Identifiants
pubmed: 35550554
pii: jitc-2022-004574
doi: 10.1136/jitc-2022-004574
pmc: PMC9109124
pii:
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: AP, NK and SPK were supported by imCORE, F. Hoffmann-La Roche. MP is an employee of F. Hoffmann-La Roche. DEG has been on advisory board for Amgen, Q Biotics, Provectus and Bayer. SS has been receiving advisory board fees, paid to her institution, and grant support from AstraZeneca and Merck Sharp & Dohme, and grant support from Amgen, Endocyte, and Genentech.
Références
Sci Rep. 2018 Jul 24;8(1):11158
pubmed: 30042403
Melanoma Res. 2020 Dec;30(6):533-542
pubmed: 33156594
Cell. 2017 Nov 2;171(4):934-949.e16
pubmed: 29033130
Bioinformatics. 2010 Jun 15;26(12):1572-3
pubmed: 20427518
Nat Commun. 2019 Jul 18;10(1):3163
pubmed: 31320640
J Exp Med. 2019 Sep 2;216(9):2128-2149
pubmed: 31227543
Nat Commun. 2018 Oct 16;9(1):4297
pubmed: 30327458
J Clin Oncol. 2007 Mar 1;25(7):869-75
pubmed: 17327608
Nature. 2015 Apr 16;520(7547):373-7
pubmed: 25754329
Cell. 2019 Jun 13;177(7):1888-1902.e21
pubmed: 31178118
Sci Immunol. 2017 Apr 14;2(10):
pubmed: 28738020
Nat Commun. 2019 Sep 27;10(1):4401
pubmed: 31562311
Cell Rep Med. 2020 Oct 20;1(7):100127
pubmed: 33205076
Nat Med. 2019 Aug;25(8):1251-1259
pubmed: 31359002
Nat Commun. 2017 Oct 26;8(1):1136
pubmed: 29070816
Nat Med. 2018 Jul;24(7):986-993
pubmed: 29942092
Urol Oncol. 2016 Apr;34(4):166.e7-14
pubmed: 26739672
Nat Immunol. 2019 Mar;20(3):326-336
pubmed: 30778252
Front Oncol. 2018 Aug 21;8:322
pubmed: 30186768
J Allergy Clin Immunol. 2018 Aug;142(2):647-662
pubmed: 29128674
Cell. 2019 Feb 7;176(4):775-789.e18
pubmed: 30595452
Methods Enzymol. 2020;632:521-543
pubmed: 32000913
Cancer Immunol Res. 2019 May;7(5):784-796
pubmed: 30872264
Nat Commun. 2018 Jul 13;9(1):2724
pubmed: 30006565
Int J Clin Exp Pathol. 2012;5(8):739-53
pubmed: 23071856
Gynecol Oncol. 2021 Jun;161(3):645-652
pubmed: 33795130
Cancer. 2017 Apr 15;123(8):1333-1344
pubmed: 28026870
Sci Immunol. 2021 Jan 29;6(55):
pubmed: 33514641
J Clin Oncol. 2017 Jan 10;35(2):226-235
pubmed: 28056206
JCI Insight. 2016 Dec 22;1(21):e88955
pubmed: 28018970
J Pathol. 2013 Jul;230(3):261-9
pubmed: 23620124
Bioinformatics. 2016 Sep 15;32(18):2847-9
pubmed: 27207943
Curr Opin Oncol. 2014 Sep;26(5):508-13
pubmed: 25046205
N Engl J Med. 2012 Mar 8;366(10):925-31
pubmed: 22397654
Clin Immunol. 2000 Aug;96(2):94-9
pubmed: 10900156
J Natl Cancer Inst. 1994 Aug 3;86(15):1159-66
pubmed: 8028037
Cytometry A. 2015 Jul;87(7):636-45
pubmed: 25573116
Nature. 2020 Mar;579(7798):274-278
pubmed: 32103181
Histopathology. 2015 Oct;67(4):548-56
pubmed: 25809697
Clin Cancer Res. 2018 Jul 1;24(13):3036-3045
pubmed: 29599411