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Identification of a novel PD-L1 positive solid tumor transplantable in HLA-A*0201/DRB1*0101 transgenic mice
- Source :
- Oncotarget, Oncotarget, Impact journals, 2017, 8 (30), pp.48959-48971. ⟨10.18632/oncotarget.16900⟩, Oncotarget, 2017, 8 (30), pp.48959-48971. ⟨10.18632/oncotarget.16900⟩, Oncotarget, Impact journals, 2017, 8 (30), pp.48959-48971. 〈http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path=16900&pubmed-linkout=1〉. 〈10.18632/oncotarget.16900〉
- Publication Year :
- 2017
- Publisher :
- Impact Journals, LLC, 2017.
-
Abstract
- IF 5.168; International audience; HLA-A*0201/DRB1*0101 transgenic mice (A2/DR1 mice) have been developed to study the immunogenicity of tumor antigen-derived T cell epitopes. To extend the use and application of this mouse model in the field of antitumor immunotherapy, we described a tumor cell line generated from a naturally occurring tumor in A2/DR1 mouse named SARC-L1. Histological and genes signature analysis supported the sarcoma origin of this cell line. While SARC-L1 tumor cells lack HLA-DRB1*0101 expression, a very low expression of HLA-A*0201 molecules was found on these cells. Furthermore they also weakly but constitutively expressed the programmed death-ligand 1 (PD-L1). Interestingly both HLA-A*0201 and PD-L1 expressions can be increased on SARC-L1 after IFN-γ exposure in vitro. We also obtained two genetically modified cell lines highly expressing either HLA-A*0201 or both HLA-A*0201/ HLA-DRB1*0101 molecules referred as SARC-A2 and SARC-A2DR1 respectively. All the SARC-L1-derived cell lines induced aggressive subcutaneous tumors in A2DR1 mice in vivo. The analysis of SARC-L1 tumor microenvironment revealed a strong infiltration by T cells expressing inhibitory receptors such as PD-1 and TIM-3. Finally, we found that SARC-L1 is sensitive to several drugs commonly used to treat sarcoma and also susceptible to anti-PD-L1 monoclonal antibody therapy in vivo. Collectively, we described a novel syngeneic tumor model A2/DR1 mice that could be used as preclinical tool for the evaluation of antitumor immunotherapies.
- Subjects :
- Male
0301 basic medicine
sarcoma
medicine.medical_treatment
Gene Expression
Apoptosis
B7-H1 Antigen
[ SDV.CAN ] Life Sciences [q-bio]/Cancer
Mice
0302 clinical medicine
Cancer immunotherapy
Neoplasms
Monoclonal antibody therapy
biology
3. Good health
Oncology
030220 oncology & carcinogenesis
[SDV.IMM]Life Sciences [q-bio]/Immunology
Female
Research Paper
PD-L1
Genetically modified mouse
[SDV.IMM] Life Sciences [q-bio]/Immunology
Cell Survival
T cells
Antineoplastic Agents
Mice, Transgenic
[SDV.CAN]Life Sciences [q-bio]/Cancer
03 medical and health sciences
Lymphocytes, Tumor-Infiltrating
[SDV.CAN] Life Sciences [q-bio]/Cancer
In vivo
Cell Line, Tumor
HLA-A2 Antigen
HLA transgenic mouse
medicine
Animals
Humans
Tumor microenvironment
cancer immunotherapy
business.industry
Gene Expression Profiling
Disease Models, Animal
030104 developmental biology
Cell culture
Immunology
biology.protein
Cancer research
business
HLA-DRB1 Chains
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....bb98cb97c189b51636ddc05b8ae94730