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SRX20928450: GSM7567373: Nko2_1; Mus musculus; RNA-Seq
1 ILLUMINA (Illumina HiSeq 4000) run: 28.5M spots, 8.5G bases, 2.5Gb downloads

External Id: GSM7567373_r1
Submitted by: Duke University
Study: Breaking through NGF-TrkA immunosuppression in melanoma sensitizes immunotherapy for durable memory T cell protection [RNA-Seq 1]
show Abstracthide Abstract
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: 1,000,000 B16F10 cells were subcutaneously injected into C57BL/6J mice. Total RNA was extracted from melanoma tissues on day 15 and analyzed by RNA-seq. There were two grops: Control sgRNA group (C1-4) and NGF sgRNA group(Nko1-4); each had 4 biological replicates.
Sample: Nko2_1
SAMN36345324 • SRS18204354 • All experiments • All runs
Organism: Mus musculus
Library:
Name: GSM7567373
Instrument: Illumina HiSeq 4000
Strategy: RNA-Seq
Source: TRANSCRIPTOMIC
Selection: cDNA
Layout: PAIRED
Construction protocol: Total RNA was extrated using a kit from ZYMO RESEARCH (Direct-zol RNA miniprep, cat. No. R2052) according to the manufacturer's instructions and dissolved in RNase-free water. Sequencing libraries were prepared using the NEB Next Ultra RNA Library Prep Kit for Illumina (NEB) according to the manufacturer's protocol. Libraries were sequenced using an Illumina HiSeq machine and paired-end reads were generated.
Runs: 1 run, 28.5M spots, 8.5G bases, 2.5Gb
Run# of Spots# of BasesSizePublished
SRR2518068828,486,1358.5G2.5Gb2023-11-02

ID:
28361301

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