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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 01, 2023 |
| Title |
Immune checkpoint inhibitor monotherapy is sufficient to promote microenvironmental normalization via Type I interferon pathway in PD-L1+ expressing head and neck cancer |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Immune checkpoint blockers (ICBs) targeting programmed death 1(PD-1) are considered effective first-line therapy against PD-1 ligand (PD-L1)-expressing head and neck squamous cell carcinoma (HNSCC). However, associated changes in tumor microenvironment (TME) and mechanisms remain elusive. Oral tumors in C57/BL6 mice were induced by administering 7,12-dimethylbenzanthracene into the buccal mucosa. Single-cell suspension was isolated from tumor tissue; proliferating cells were injected subcutaneously into the left flank of mice to establish Ajou Oral Cancer (AOC) cell lines. Subsequently, a syngeneic PD-L1-expressing HNSCC xenograft model was developed by injecting AOC cells into the buccal or tongue area. The model recapitulated human HNSCC molecular features and showed reliable in vivo tumorigenicity with significant PD-L1 expression. ICB monotherapy induced global changes in TME, including vascular normalization. Furthermore, the anti-tumor effect of ICB monotherapy was superior to those of other therapeutic agents, including cisplatin and anti-vascular endothelial growth factor receptor 2 inhibitors. The ICB-induced anti-tumorigenicity and TME normalization were alleviated by blocking the Type I interferon pathway.In summary, ICB monotherapy is sufficient to induce TME normalization in the syngeneic model; the Type-I interferon pathway is indispensable in realizing ICB effects. Furthermore, these results explain the underlying mechanism of the efficacy of ICB monotherapy against HNSCC expressing PD-L1 in the KEYNOTE-048 trial. This model can assist future research on HNSCC immunotherapy.
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| Overall design |
Transcriptome profiling from 4 cell lines of Ajou Oral Cancer (AOC, n=2) and 2 metastatic lymph node tumors (LNC, n=2)
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| Contributor(s) |
Jang JY, Lee B, Huang M, Seo C, Choi J, Shin YS, Woo HG, Kim C |
| Citation(s) |
38511232 |
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| Submission date |
Nov 20, 2023 |
| Last update date |
Sep 05, 2024 |
| Contact name |
Ji-Hye Choi |
| E-mail(s) |
jihea0122@gmail.com
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| Phone |
01055455183
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| Organization name |
Ajou university
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| Street address |
World cup-ro
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| City |
Suwon-si |
| State/province |
Gyeonggi-do |
| ZIP/Postal code |
16499 |
| Country |
South Korea |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1043139 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE248271_FPKM_expression.txt.gz |
932.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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