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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 01, 2021 |
| Title |
Targeting IL-21 to tumor-reactive T cells enhances memory T cell responses and anti-PD-1 antibody therapy |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
T cell rejuvenation by PD-1/PD-L1 blockade, despite emerging as a highly promising therapy for advanced cancers, is only beneficial for a minority of treated patients. There is evidence that a lack of efficient T cell activation may be responsible for the failure. Here, we demonstrate that IL-21 can be targeted to tumor-reactive T cells by fusion of IL-21 to anti-PD-1 antibody. To our surprise, the fusion protein PD-1Ab21 promoted the generation of TSCM-like CD8+ T cells with enhanced cell proliferation. A transcriptome analysis of isolated TN, activated and PD-1Ab-cultured CD44highCD62Lhigh T cells, IL-2-generated TE/TEM, IL-15-generated TCM as well as PD-1Ab21 and IL-21-generated CD44lowCD62Lhigh T cells provides corroborating evidence that PD-1Ab21 induces conversion of activated CD8+ T cells back to a memory subset that is distinct from TCM cells, but similar to TSCM. PD-1Ab21 treatment showed potent antitumor effects in established tumor-bearing mice accompanied with an increased frequency of TSCM and robust expansion of tumor-specific CD8+ T cells with a memory phenotype, and was superior to a combination of PD-1 blockade and IL-21 infusion. Therefore, we have developed a potential strategy to improve the therapeutic effects of immune checkpoint blockade by simultaneously targeting cytokines to tumor-reactive T cells.
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| Overall design |
mRNA profiles of naïve, OVA-activated, IL-2-,IL-15-, IL-21-, PD-1Ab-, PD-1Ab-21-differentiated OT-1 T cells in vitro. Totally 21 samples were sequencing, 3 replicates per group.
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| Contributor(s) |
Li Y, Jia M, Wang S |
| Citation(s) |
33574265 |
| Submission date |
Dec 31, 2020 |
| Last update date |
Mar 02, 2021 |
| Contact name |
Ying Li |
| E-mail(s) |
liy@ibp.ac.cn
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| Phone |
010-64887560
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| Organization name |
Institute of Biophysics, Chinese Academy of Sciences
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| Street address |
Datun Road #15, Chaoyang District
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| City |
Beijing |
| ZIP/Postal code |
100101 |
| Country |
China |
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| Platforms (1) |
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| Samples (21)
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| Relations |
| BioProject |
PRJNA688889 |
| SRA |
SRP299895 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE164093_RAW.tar |
1.5 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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