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Series GSE236674 Query DataSets for GSE236674
Status Public on Nov 02, 2023
Title Breaking through NGF-TrkA immunosuppression in melanoma sensitizes immunotherapy for durable memory T cell protection [RNA-Seq 2]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Melanomas are generated from melanocytes, the neural crest derivatives sharing a neuroectodermal origin with the nervous system. In investigating whether immune privilege of the nervous system might be exploited by melanoma, we found that nerve growth factor (NGF) exerts both melanoma cell-intrinsic and -extrinsic immunosuppression. In melanoma cells, autocrine NGF engages TrkA receptor to desensitize IFN-gammasignaling, leading to T and NK cell exclusion. In effector T cells, which upregulate surface TrkA expression upon T cell receptor (TCR) activation, paracrine NGF dampens TCR signaling and effector function. Targeting NGF genetically or pharmacologically with larotrectinib sensitizes melanoma responsiveness to immune checkpoint blockade (ICB) therapy for tumor eradication and induces durable protection by eliciting robust memory of low-affinity T cells. Together, these findings uncover a comprehensive mechanism through which the NGF-TrkA axis suppresses anti-tumor T cell immunity, thus providing a novel mode of action to repurpose larotrectinib for immune sensitization. Moreover, by enlisting low-affinity tumor-specific T cells, anti-NGF reduces acquired resistance to ICB therapy and prevents melanoma recurrence.
 
Overall design CD8+ T cells were isolated by MACS from 6-8 week old C57BL/6 mice, and activated by plate-bound anti-CD3/28 antibodies. 72 hr later, activated CD8+ T cells were further treated by 200 ng/ml recombinant murine NGF for another 24 hr. Cells were then collected for bulk RNA-seq. There were two groups, including control (C1-3) and NGF-treatment group (mNGF1-3); each was triplicated.
 
Contributor(s) Yin T, Wang L, Mudgal P, Li Q, Wang X
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Jul 06, 2023
Last update date Nov 02, 2023
Contact name Liuyang Wang
Organization name Duke University
Street address 213 Research Drive
City Durham
State/province NC
ZIP/Postal code 27710
Country USA
 
Platforms (1)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (6)
GSM7567376 C_1 (biol rep 1)
GSM7567377 C_2 (biol rep 2)
GSM7567378 C_3 (biol rep 3)
This SubSeries is part of SuperSeries:
GSE236682 Breaking through NGF-TrkA immunosuppression in melanoma sensitizes immunotherapy for durable memory T cell protection
Relations
BioProject PRJNA992003

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE236674_Tao_NGF_featurecount_matrix.txt.gz 4.0 Mb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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