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Series GSE260791 Query DataSets for GSE260791
Status Public on Jun 12, 2024
Title Correction of age-associated defects in dendritic cell functions enables CD4+T cells to eradicate tumors in the elderly
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Defective host defenses later in life are associated with changes in immune system activity. The means to correct immune defects to ensure immunity in the elderly are undefined. In this study, we found that CD8+T cells, which are necessary for anti-tumor immunity in young mice, are not required to eradicate the same cancers later in life. Rather, CD4+T cells drive anti-tumor immunity in elderly mice. The generation of anti-tumor CD4+T cells requires multiple dendritic cell (DC) activities that are elicited by immune agonists known as hyperactivators, but not by adjuvants that model those used clinically. DC hyperactivators correct age-associated defects in DC migration and T cell co-stimulation while enabling NLRP3 inflammasome activities within living cells. These combined activities enable DCs to induce TH1-skewed T cells that persist into old age and eliminate implantable tumors. These results raise the possibility of correcting age-associated immune defects through DC manipulation.
 
Overall design 8 weeks or 92 weeks old mice were immunized with either PBS or OVA+LPS+PGPC. Mice received two boost injections every 7 days. 21 days post immunization, spleen samples were subjected to CD3e T cell enrichment to achieve highly pure (>85%) of CD3+ T cells. We then generated scRNA-seq data from splenic T cells using the NovaSeqX platform to explore the transcriptomic differences between the age groups.
 
Contributor(s) Park J, Ashenberg O, Kagan JC, Zhivaki D
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Submission date Mar 04, 2024
Last update date Jun 12, 2024
Contact name Ramnik Xavier
E-mail(s) xaviergeo@broadinstitute.org
Organization name Broad Institute of MIT and Harvard
Lab Xavier Lab
Street address 415 Main Street
City Cambridge
State/province MA
ZIP/Postal code 02142
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (30)
GSM8124640 8wk-PBS-Only-Mouse-1
GSM8124641 8wk_PBS_Only_Mouse_2
GSM8124642 8wk_PBS_Only_Mouse_3
Relations
BioProject PRJNA1083511

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Supplementary file Size Download File type/resource
GSE260791_crmulti_gex_raw.h5ad.gz 277.0 Mb (ftp)(http) H5AD
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Raw data are available in SRA

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