Vincristine upregulates PD-L1 and increases the efficacy of PD-L1 blockade therapy in diffuse large B-cell lymphoma.
Animals
Antineoplastic Agents, Immunological
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ pharmacology
B7-H1 Antigen
/ antagonists & inhibitors
Cell Line, Tumor
Drug Synergism
Female
Humans
Lymphoma, Large B-Cell, Diffuse
/ drug therapy
Mice
Mice, Inbred BALB C
Mice, Nude
Random Allocation
Up-Regulation
/ drug effects
Vincristine
/ administration & dosage
Xenograft Model Antitumor Assays
Diffuse large B-cell lymphoma
Immunotherapy
Programed cell death-ligand 1
Programmed cell death-1
Vincristine
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Mar 2021
Mar 2021
Historique:
received:
25
07
2020
accepted:
28
10
2020
pubmed:
4
1
2021
medline:
25
2
2021
entrez:
3
1
2021
Statut:
ppublish
Résumé
Some chemotherapy drugs have immunomodulatory effects on specific tumors. The potential of vincristine (VCR) in the R-CHOP regimen to act as both a chemotherapeutic and an immunomodulatory agent via PD-L1 in tumor cells remains unclear. In vitro screening VCR showed that the IC50 value of VCR in the DLBCL cell lines was approximately 2 nM. Western blotting and q-PCR were used to detect the expression of PD-L1. The effect of VCR combined with PD-L1 mAb was tested in a co-culture system of LY-OCI-3 cells and peripheral blood mononuclear cells and in DLBCL xenograft mouse model. Flow cytometry was used to determine the proportion of T lymphocyte subsets. The effect of the STAT3 inhibitor nifuroxazide on VCR-induced PD-L1 expression was tested in LY-OCI-3 and SU-DHL-4 cells. VCR upregulated PD-L1 protein and mRNA expression in various DLBCL cell lines. PD-L1 Ab combined with VCR significantly increased the proportion of CD8 + Granzyme B + , INF-γ + or TNF-α + CD3 + T cells. VCR + PD-L1 Ab inhibited tumor growth more effectively than VCR monotherapy, whereas PD-L1 Ab alone had no significant effect. Survival time did not differ significantly between the PD-L1 Ab group and the control group, whereas it was significantly longer in the VCR monotherapy and combination groups which showed more longer survival compared with the former. Nifuroxazide downregulated p-STAT3 and PD-L1 protein levels. VCR upregulated PD-L1 expression in DLBCL cells partially by promoting the p-STAT3; VCR combined with PD-L1 Ab activated effector T cells and increased the antitumor immune response in vitro and in vivo.
Sections du résumé
BACKGROUND
BACKGROUND
Some chemotherapy drugs have immunomodulatory effects on specific tumors. The potential of vincristine (VCR) in the R-CHOP regimen to act as both a chemotherapeutic and an immunomodulatory agent via PD-L1 in tumor cells remains unclear.
METHODS
METHODS
In vitro screening VCR showed that the IC50 value of VCR in the DLBCL cell lines was approximately 2 nM. Western blotting and q-PCR were used to detect the expression of PD-L1. The effect of VCR combined with PD-L1 mAb was tested in a co-culture system of LY-OCI-3 cells and peripheral blood mononuclear cells and in DLBCL xenograft mouse model. Flow cytometry was used to determine the proportion of T lymphocyte subsets. The effect of the STAT3 inhibitor nifuroxazide on VCR-induced PD-L1 expression was tested in LY-OCI-3 and SU-DHL-4 cells.
RESULTS
RESULTS
VCR upregulated PD-L1 protein and mRNA expression in various DLBCL cell lines. PD-L1 Ab combined with VCR significantly increased the proportion of CD8 + Granzyme B + , INF-γ + or TNF-α + CD3 + T cells. VCR + PD-L1 Ab inhibited tumor growth more effectively than VCR monotherapy, whereas PD-L1 Ab alone had no significant effect. Survival time did not differ significantly between the PD-L1 Ab group and the control group, whereas it was significantly longer in the VCR monotherapy and combination groups which showed more longer survival compared with the former. Nifuroxazide downregulated p-STAT3 and PD-L1 protein levels.
CONCLUSIONS
CONCLUSIONS
VCR upregulated PD-L1 expression in DLBCL cells partially by promoting the p-STAT3; VCR combined with PD-L1 Ab activated effector T cells and increased the antitumor immune response in vitro and in vivo.
Identifiants
pubmed: 33389078
doi: 10.1007/s00432-020-03446-w
pii: 10.1007/s00432-020-03446-w
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
B7-H1 Antigen
0
CD274 protein, human
0
Cd274 protein, mouse
0
Vincristine
5J49Q6B70F
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
691-701Subventions
Organisme : Guangzhou Planned Project of Science and Technology
ID : 201707010279
Organisme : The Nature Science Foundation of China
ID : 81671632
Organisme : The Nature Science Foundation of China
ID : 81874169
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