Chemotherapy Shifts the Balance in Favor of CD8+ TNFR2+ TILs in Triple-Negative Breast Tumors.
Adult
Aged
Aged, 80 and over
Animals
Biomarkers, Tumor
/ metabolism
CD4-Positive T-Lymphocytes
/ drug effects
CD8-Positive T-Lymphocytes
/ drug effects
Cell Line, Tumor
Cohort Studies
Disease-Free Survival
Female
Humans
Lymphocytes, Tumor-Infiltrating
/ drug effects
Mice
Mice, Inbred BALB C
Middle Aged
Prognosis
Receptors, Tumor Necrosis Factor, Type II
/ metabolism
Triple Negative Breast Neoplasms
/ drug therapy
CD4+ lymphocytes
CD8+ lymphocytes
forkhead box P3 (FOXP3)
programmed cell death protein 1 (PD-1)
splenocytes
triple-negative breast cancer (TNBC)
tumor necrosis factor receptor 2 (TNFR2)
tumor necrosis factor α (TNFα)
tumor-infiltrating lymphocytes (TILs)
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
08 06 2021
08 06 2021
Historique:
received:
28
04
2021
revised:
31
05
2021
accepted:
02
06
2021
entrez:
2
7
2021
pubmed:
3
7
2021
medline:
30
10
2021
Statut:
epublish
Résumé
Triple-negative breast cancer (TNBC) is primarily treated via chemotherapy; in parallel, efforts are made to introduce immunotherapies into TNBC treatment. CD4+ TNFR2+ lymphocytes were reported as Tregs that contribute to tumor progression. However, our published study indicated that TNFR2+ tumor-infiltrating lymphocytes (TNFR2+ TILs) were associated with improved survival in TNBC patient tumors. Based on our analyses of the contents of CD4+ and CD8+ TILs in TNBC patient tumors, in the current study, we determined the impact of chemotherapy on CD4+ and CD8+ TIL subsets in TNBC mouse tumors. We found that chemotherapy led to (1) a reduction in CD4+ TNFR2+ FOXP3+ TILs, indicating that chemotherapy decreased the content of CD4+ TNFR2+ Tregs, and (2) an elevation in CD8+ TNFR2+ and CD8+ TNFR2+ PD-1+ TILs; high levels of these two subsets were significantly associated with reduced tumor growth. In spleens of tumor-bearing mice, chemotherapy down-regulated CD4+ TNFR2+ FOXP3+ cells but the subset of CD8+ TNFR2+ PD-1+ was not present prior to chemotherapy and was not increased by the treatment. Thus, our data suggest that chemotherapy promotes the proportion of protective CD8+ TNFR2+ TILs and that, unlike other cancer types, therapeutic strategies directed against TNFR2 may be detrimental in TNBC.
Identifiants
pubmed: 34201054
pii: cells10061429
doi: 10.3390/cells10061429
pmc: PMC8229590
pii:
doi:
Substances chimiques
Biomarkers, Tumor
0
Receptors, Tumor Necrosis Factor, Type II
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Israel Cancer Research Fund
ID : N/A
Organisme : Federico Foundation
ID : N/A
Références
Nat Immunol. 2011 Jun;12(6):492-9
pubmed: 21739672
Cell Death Differ. 2003 Jan;10(1):45-65
pubmed: 12655295
J Immunother Cancer. 2019 Feb 6;7(1):34
pubmed: 30728081
Breast Care (Basel). 2016 Dec;11(6):385-390
pubmed: 28228704
Clin Cancer Res. 2017 Aug 1;23(15):4416-4428
pubmed: 28213366
BMC Cancer. 2018 Feb 2;18(1):123
pubmed: 29390966
Hum Pathol. 2017 Jun;64:7-12
pubmed: 28153508
Nat Rev Dis Primers. 2019 Sep 23;5(1):66
pubmed: 31548545
Cancers (Basel). 2020 Nov 26;12(12):
pubmed: 33256070
Cancer Immunol Immunother. 2020 Feb;69(2):263-273
pubmed: 31820042
Front Immunol. 2019 Aug 28;10:2040
pubmed: 31555271
N Engl J Med. 2018 Nov 29;379(22):2108-2121
pubmed: 30345906
BMC Cancer. 2011 Apr 12;11:130
pubmed: 21486440
Sci Signal. 2017 Jan 17;10(462):
pubmed: 28096506
Mod Pathol. 2018 Oct;31(10):1513-1522
pubmed: 29802358
Ann Oncol. 2014 Aug;25(8):1544-50
pubmed: 24608200
Cancer Res. 2015 Dec 15;75(24):5235-47
pubmed: 26483205
Nat Med. 2019 Jun;25(6):920-928
pubmed: 31086347
Int Immunopharmacol. 2011 Oct;11(10):1489-96
pubmed: 21635972
Sci Transl Med. 2019 Oct 2;11(512):
pubmed: 31578241
J Leukoc Biol. 2015 Sep;98(3):423-34
pubmed: 26019295
Cell. 1995 Dec 1;83(5):793-802
pubmed: 8521496
Cold Spring Harb Perspect Biol. 2018 Aug 1;10(8):
pubmed: 28778871
Nat Rev Clin Oncol. 2016 Nov;13(11):674-690
pubmed: 27184417
Oncotarget. 2016 Oct 18;7(42):68278-68291
pubmed: 27626702
Breast Cancer (Auckl). 2018 May 30;12:1178223418774802
pubmed: 29899661
Sci Signal. 2017 Jan 17;10(462):
pubmed: 28096513
J Oncol. 2019 May 23;2019:6313242
pubmed: 31239840
Cancer Immunol Res. 2015 May;3(5):436-43
pubmed: 25941355
Oncology (Williston Park). 2017 Feb 15;31(2):130-7
pubmed: 28205193
Br J Pharmacol. 2002 Feb;135(4):855-75
pubmed: 11861313
J Clin Invest. 2014 May;124(5):2246-59
pubmed: 24667641
Cell Oncol (Dordr). 2020 Feb;43(1):1-18
pubmed: 31900901
Oncoimmunology. 2015 Jul 27;4(9):e985930
pubmed: 26405612
Cancer Immunol Immunother. 2020 Jul;69(7):1315-1326
pubmed: 32198536
Breast Cancer Res Treat. 2018 Feb;167(3):671-686
pubmed: 29063313
Oncotarget. 2017 Feb 28;8(9):15584-15592
pubmed: 28107186
ESMO Open. 2018 May 3;3(Suppl 1):e000357
pubmed: 29765774
J Immunol. 2009 Nov 15;183(10):6051-7
pubmed: 19841176
Rheumatology (Oxford). 2010 Jul;49(7):1215-28
pubmed: 20194223
Front Immunol. 2018 May 28;9:1170
pubmed: 29892300
Sci Signal. 2020 Dec 08;13(661):
pubmed: 33293464
Oncoimmunology. 2015 Apr 16;4(10):e1040215
pubmed: 26451304
Trends Mol Med. 2017 Nov;23(11):1037-1046
pubmed: 29032004
Front Immunol. 2019 Sep 06;10:2126
pubmed: 31555303
Immunology. 2010 Apr;129(4):474-81
pubmed: 20201977
J Immunol. 2008 May 15;180(10):6467-71
pubmed: 18453563
Sci Signal. 2018 Jan 02;11(511):
pubmed: 29295954
Cancer Immunol Immunother. 2015 Nov;64(11):1475-85
pubmed: 26280204
Clin Cancer Res. 2008 Apr 15;14(8):2413-20
pubmed: 18413832
Front Immunol. 2017 Nov 28;8:1675
pubmed: 29234328
Breast Cancer Res. 2007;9(1):R15
pubmed: 17261184
Front Immunol. 2013 Dec 23;4:478
pubmed: 24391650
Eur J Immunol. 2020 Jul;50(7):972-985
pubmed: 32012260
J Immunol Res. 2014;2014:286170
pubmed: 24868562
Ann Oncol. 2012 Aug;23 Suppl 6:vi46-51
pubmed: 23012302
Nat Rev Immunol. 2015 Aug;15(8):486-99
pubmed: 26205583
Exp Mol Pathol. 2007 Feb;82(1):12-24
pubmed: 16919266
J Biomed Sci. 2017 Dec 04;24(1):90
pubmed: 29202842
J Leukoc Biol. 2020 Jun;107(6):981-991
pubmed: 32449229
Clin Cancer Res. 2017 Jun 1;23(11):2640-2646
pubmed: 28572258
J Immunol. 2010 Jul 1;185(1):174-82
pubmed: 20525892
Eur J Immunol. 2010 Apr;40(4):1099-106
pubmed: 20127680
Clin Immunol. 2008 Nov;129(2):219-29
pubmed: 18771959
Clin Cancer Res. 2016 Apr 15;22(8):1856-64
pubmed: 27084739
Cancer. 1997 Aug 1;80(3):421-34
pubmed: 9241076
Cancer Treat Rev. 2012 Oct;38(6):698-707
pubmed: 22178455
Front Immunol. 2018 Mar 22;9:583
pubmed: 29623079
Nat Rev Clin Oncol. 2011 Mar;8(3):151-60
pubmed: 21364688
JAMA Oncol. 2019 Jan 1;5(1):74-82
pubmed: 30242306
Nat Rev Cancer. 2009 May;9(5):361-71
pubmed: 19343034
J Immunother Cancer. 2019 Feb 4;7(1):28
pubmed: 30717817
Oncol Lett. 2017 Aug;14(2):1766-1774
pubmed: 28789407