Combined Blockade Of PD-1 and TIGIT is not Sufficient to Improve the Function Of CD8+ T-Cells in Chronic Lymphocytic Leukemia.
Chronic Lymphocytic Leukemia
PD-1
T-cell exhaustion
TIGIT
immune checkpoint blockade
Journal
Asian Pacific journal of cancer prevention : APJCP
ISSN: 2476-762X
Titre abrégé: Asian Pac J Cancer Prev
Pays: Thailand
ID NLM: 101130625
Informations de publication
Date de publication:
01 Jul 2022
01 Jul 2022
Historique:
received:
13
03
2021
entrez:
28
7
2022
pubmed:
29
7
2022
medline:
2
8
2022
Statut:
epublish
Résumé
Blockade of immune checkpoint receptors in the treatment of cancers has been mentioned in several studies. Here, we investigated the efficacy of combined blockade of two inhibitory receptors, PD-1 and TIGIT, in restoring functional features of CD8+ T-cells in CLL. CD8+ T-cells were separated from the peripheral blood of 11 CLL patients and targeted with malignant B-cells isolated from the same patients. Cells were then stimulated with anti-CD3/CD28 and PMA/ionomycin to assess their proliferative response and cytotoxic activity using MTT and CD107a degranulation assays, respectively. Cytokine production of isolated CD8+ T-cells was also determined using ELISA. There were no significant differences in proliferation and cytotoxic activity of CD8+ T-cells co-blocked with anti-PD-1/TIGIT compared to those single blocked with anti-PD-1, anti-TIGIT, or the control antibody. There was no significant difference in cytokine production of mentioned groups, either. Collectively, combined blockade of PD-1 and TIGIT failed to restore the proliferation and function of CD8+ T-cells isolated from CLL patients.
Sections du résumé
BACKGROUND AND OBJECTIVE
OBJECTIVE
Blockade of immune checkpoint receptors in the treatment of cancers has been mentioned in several studies. Here, we investigated the efficacy of combined blockade of two inhibitory receptors, PD-1 and TIGIT, in restoring functional features of CD8+ T-cells in CLL.
METHODS
METHODS
CD8+ T-cells were separated from the peripheral blood of 11 CLL patients and targeted with malignant B-cells isolated from the same patients. Cells were then stimulated with anti-CD3/CD28 and PMA/ionomycin to assess their proliferative response and cytotoxic activity using MTT and CD107a degranulation assays, respectively. Cytokine production of isolated CD8+ T-cells was also determined using ELISA.
RESULTS
RESULTS
There were no significant differences in proliferation and cytotoxic activity of CD8+ T-cells co-blocked with anti-PD-1/TIGIT compared to those single blocked with anti-PD-1, anti-TIGIT, or the control antibody. There was no significant difference in cytokine production of mentioned groups, either.
CONCLUSIONS
CONCLUSIONS
Collectively, combined blockade of PD-1 and TIGIT failed to restore the proliferation and function of CD8+ T-cells isolated from CLL patients.
Identifiants
pubmed: 35901326
doi: 10.31557/APJCP.2022.23.7.2225
pmc: PMC9727349
pii:
doi:
Substances chimiques
Cytokines
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Receptors, Immunologic
0
TIGIT protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2225-2231Références
Blood. 2013 Feb 28;121(9):1612-21
pubmed: 23247726
J Hematol Oncol. 2018 Mar 2;11(1):33
pubmed: 29495966
Blood. 2015 Jul 9;126(2):203-11
pubmed: 25800048
Nat Rev Immunol. 2015 Jan;15(1):45-56
pubmed: 25534622
Nature. 2006 Sep 21;443(7109):350-4
pubmed: 16921384
Nat Med. 2006 Oct;12(10):1198-202
pubmed: 16917489
Hematology Am Soc Hematol Educ Program. 2008;:457-64
pubmed: 19074126
Rinsho Ketsueki. 2017;58(10):1960-1972
pubmed: 28978838
Haematologica. 2021 Apr 01;106(4):968-977
pubmed: 32139435
Oncologist. 1999;4(5):352-69
pubmed: 10551552
N Engl J Med. 2015 Jan 22;372(4):311-9
pubmed: 25482239
Blood Adv. 2019 Sep 10;3(17):2642-2652
pubmed: 31506282
Leukemia. 2019 Mar;33(3):625-637
pubmed: 30267008
J Clin Invest. 2015 May;125(5):2046-58
pubmed: 25866972
Iran J Allergy Asthma Immunol. 2021 Dec 08;20(6):751-763
pubmed: 34920658
Oncoimmunology. 2018 May 24;7(8):e1466769
pubmed: 30221069
Immunol Res. 2020 Oct;68(5):269-279
pubmed: 32710227
Haematologica. 2017 May;102(5):874-882
pubmed: 28154084
Cancer Res. 2013 Jun 15;73(12):3591-603
pubmed: 23633484
Oncology (Williston Park). 2016 Jun;30(6):526-33, 540
pubmed: 27311839
J Invest Dermatol. 2016 Jan;136(1):255-63
pubmed: 26763445
Lancet Oncol. 2016 Jul;17(7):956-965
pubmed: 27247226
Curr Hematol Malig Rep. 2016 Feb;11(1):29-36
pubmed: 26857283
Cancers (Basel). 2020 Mar 20;12(3):
pubmed: 32245016
Immunity. 2016 May 17;44(5):989-1004
pubmed: 27192565
N Engl J Med. 2013 Jul 11;369(2):134-44
pubmed: 23724846
Eur J Cancer Care (Engl). 2004 Jul;13(3):279-87
pubmed: 15196232