Immunotherapy Goes Local: The Central Role of Lymph Nodes in Driving Tumor Infiltration and Efficacy.
CTLA-4
PD-1
cancer
dendritic cell
immune check point
immune exclusion
t cell exhaustion
tumor draining lymph node
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
17
12
2020
accepted:
09
02
2021
entrez:
18
3
2021
pubmed:
19
3
2021
medline:
24
9
2021
Statut:
epublish
Résumé
Immune checkpoint blockade (ICB) has changed the therapeutic landscape of oncology but its impact is limited by primary or secondary resistance. ICB resistance has been related to a lack of T cells infiltrating into the tumor. Strategies to overcome this hurdle have so far focused on the tumor microenvironment, but have mostly overlooked the role of tumor-draining lymph nodes (TDLN). Whereas for CTLA-4 blockade TDLN have long since been implicated due to its perceived mechanism-of-action involving T cell priming, only recently has evidence been emerging showing TDLN to be vital for the efficacy of PD-1 blockade as well. TDLN are targeted by developing tumors to create an immune suppressed pre-metastatic niche which can lead to priming of dysfunctional antitumor T cells. In this review, we will discuss the evidence that therapeutic targeting of TDLN may ensure sufficient antitumor T cell activation and subsequent tumor infiltration to facilitate effective ICB. Indeed, waves of tumor-specific, proliferating stem cell-like, or progenitor exhausted T cells, either newly primed or reinvigorated in TDLN, are vital for PD-1 blockade efficacy. Both tumor-derived migratory dendritic cell (DC) subsets and DC subsets residing in TDLN, and an interplay between them, have been implicated in the induction of these T cells, their imprinting for homing and subsequent tumor control. We propose that therapeutic approaches, involving local delivery of immune modulatory agents for optimal access to TDLN, aimed at overcoming hampered DC activation, will enable ICB by promoting T cell recruitment to the tumor, both in early and in advanced stages of cancer.
Identifiants
pubmed: 33732264
doi: 10.3389/fimmu.2021.643291
pmc: PMC7956978
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
643291Informations de copyright
Copyright © 2021 van Pul, Fransen, van de Ven and de Gruijl.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Cancer Immunol Immunother. 2018 Nov;67(11):1767-1776
pubmed: 30167863
Nat Immunol. 2019 Mar;20(3):326-336
pubmed: 30778252
Nat Commun. 2018 May 29;9(1):2113
pubmed: 29844317
Sci Transl Med. 2020 Mar 11;12(534):
pubmed: 32161104
Cancer Cell. 2018 Apr 9;33(4):649-663.e4
pubmed: 29576375
Blood. 2011 Sep 1;118(9):2502-10
pubmed: 21750314
Immunity. 2019 Jun 18;50(6):1498-1512.e5
pubmed: 31097342
Science. 2017 Mar 31;355(6332):1423-1427
pubmed: 28280249
Nature. 2013 Aug 22;500(7463):415-21
pubmed: 23945592
Nature. 2020 Mar;579(7798):274-278
pubmed: 32103181
Clin Cancer Res. 2007 May 15;13(10):2961-9
pubmed: 17504997
Ann Oncol. 2018 Nov 1;29(11):2163-2174
pubmed: 30295695
Eur J Cancer. 2017 Sep;83:19-27
pubmed: 28709135
Front Med (Lausanne). 2019 Mar 13;6:27
pubmed: 30931305
J Immunother Cancer. 2020 Oct;8(2):
pubmed: 33046620
Cancer Immunol Res. 2017 Nov;5(11):969-977
pubmed: 28935649
Eur J Immunol. 2017 Feb;47(2):385-393
pubmed: 27873300
Oncoimmunology. 2014 Jan 1;3(1):e27400
pubmed: 24701374
Cell. 2017 Jun 29;170(1):142-157.e19
pubmed: 28648661
J Immunother Cancer. 2019 May 22;7(1):133
pubmed: 31118093
Cell. 2018 Nov 1;175(4):998-1013.e20
pubmed: 30388456
N Engl J Med. 2018 May 24;378(21):1976-1986
pubmed: 29658848
Cancer Cell. 2016 Aug 8;30(2):324-336
pubmed: 27424807
Cell Rep. 2018 Jul 10;24(2):379-390.e6
pubmed: 29996099
Immunity. 2019 Jan 15;50(1):195-211.e10
pubmed: 30635237
BMC Cancer. 2018 Sep 12;18(1):888
pubmed: 30208866
Nat Med. 2019 Mar;25(3):477-486
pubmed: 30742122
Clin Cancer Res. 2020 Jul 15;26(14):3791-3802
pubmed: 32220890
J Immunother Cancer. 2016 Mar 15;4:12
pubmed: 26981242
Lancet Oncol. 2014 Nov;15(12):1303-10
pubmed: 25439688
Sci Transl Med. 2020 Sep 30;12(563):
pubmed: 32998971
J Immunother Cancer. 2019 Feb 12;7(1):43
pubmed: 30755279
Oncoimmunology. 2013 Nov 1;2(11):e26493
pubmed: 24490127
J Clin Invest. 2013 Jun;123(6):2447-63
pubmed: 23728179
Sci Transl Med. 2017 Sep 13;9(407):
pubmed: 28904226
Nat Immunol. 2020 Dec;21(12):1552-1562
pubmed: 33046887
Nature. 2014 Nov 27;515(7528):568-71
pubmed: 25428505
Cancer Discov. 2018 Sep;8(9):1069-1086
pubmed: 30115704
Clin Cancer Res. 2008 Jul 15;14(14):4532-42
pubmed: 18628468
Science. 2017 Mar 31;355(6332):1428-1433
pubmed: 28280247
Nat Med. 2018 May;24(5):541-550
pubmed: 29686425
Cancer Immunol Immunother. 2017 Jan;66(1):1-7
pubmed: 27714433
N Engl J Med. 2017 Jun 8;376(23):2211-2222
pubmed: 28591523
Clin Cancer Res. 2014 Apr 1;20(7):1747-56
pubmed: 24691639
Cancer Cell. 2020 Jun 8;37(6):786-799.e5
pubmed: 32516589
Front Immunol. 2020 Oct 06;11:592569
pubmed: 33123174
J Immunol. 2018 Oct 1;201(7):2132-2140
pubmed: 30111633
Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):E761-E770
pubmed: 28096382
Clin Cancer Res. 2017 Oct 1;23(19):5679-5686
pubmed: 28972083
Cell. 2019 Apr 18;177(3):556-571.e16
pubmed: 30955881
Immunity. 2016 Aug 16;45(2):389-401
pubmed: 27521269
Nature. 2019 Dec;576(7787):465-470
pubmed: 31827286
Front Oncol. 2018 Feb 21;8:36
pubmed: 29527513
Lancet Oncol. 2019 Jul;20(7):948-960
pubmed: 31160251
Nat Med. 2018 Nov;24(11):1649-1654
pubmed: 30297909
Proc Natl Acad Sci U S A. 2016 Nov 15;113(46):E7240-E7249
pubmed: 27799536
Cell. 2017 Sep 7;170(6):1109-1119.e10
pubmed: 28886381
Cancer Immunol Res. 2015 May;3(5):495-505
pubmed: 25633713
Cancer Immunol Immunother. 2016 Apr;65(4):405-15
pubmed: 26935057
Nature. 2016 Sep 15;537(7620):417-421
pubmed: 27501248
Br J Cancer. 2020 Sep;123(6):885-897
pubmed: 32713938
Ann Surg Oncol. 2016 Dec;23(13):4169-4177
pubmed: 27342831
Immunity. 2016 Apr 19;44(4):924-38
pubmed: 27096321
Clin Cancer Res. 2013 Oct 1;19(19):5381-9
pubmed: 23788581
Sci Immunol. 2019 May 31;4(35):
pubmed: 31152091
Oncoimmunology. 2019 Dec 26;9(1):1708066
pubmed: 32002303
Cancer Res. 2018 Dec 1;78(23):6643-6654
pubmed: 30297531
Nature. 2015 Jul 9;523(7559):231-5
pubmed: 25970248
Nat Rev Immunol. 2018 Oct;18(10):635-647
pubmed: 30057419
Cancer Immunol Res. 2014 Jan;2(1):80-90
pubmed: 24778163
Cancer Cell. 2020 Nov 9;38(5):685-700.e8
pubmed: 33007259
Proc Natl Acad Sci U S A. 2017 May 9;114(19):4993-4998
pubmed: 28446615
JCI Insight. 2018 Dec 6;3(23):
pubmed: 30518694
Immunity. 2018 Dec 18;49(6):1148-1161.e7
pubmed: 30552023
Cancer Res. 2010 Nov 1;70(21):8378-87
pubmed: 20861189
Nat Rev Immunol. 2006 Sep;6(9):659-70
pubmed: 16932751