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Series GSE244982 Query DataSets for GSE244982
Status Public on Feb 06, 2024
Title Molecular patterns of resistance to immune checkpoint blockade in melanoma [bulk RNA-Seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Immune checkpoint blockade (ICB) has improved outcome for patients with metastatic melanoma but not all benefit from treatment. Several immune- and tumor intrinsic features are associated with clinical response at baseline. However, we need to further understand the molecular changes occurring during development of ICB resistance. Here, we collected biopsies from a cohort of 44 melanoma patients after progression to anti-CTLA4 or anti-PD1 monotherapy. Genetic alterations of antigen presentation and interferon gamma signaling pathways were observed in approximately 25% of ICB resistant cases. Anti-CTLA4 resistant lesions had a sustained immune response, including immune-regulatory features, as suggested by multiplex spatial and TCR clonality analyses. One anti-PD1 resistant lesion harbored a distinct immune cell niche, however, anti-PD1 resistant tumors were generally immune poor with non-expanded TCR clones. Such immune poor microenvironments were associated with melanoma cells having a de-differentiated phenotype lacking expression of MHC-I molecules. In addition, anti-PD1 resistant tumors had reduced fractions of PD1+ CD8+ T cells as compared to ICB naïve metastases. Collectively, these data show the complexity of ICB resistance and highlight differences between anti-CTLA4 and anti-PD1 resistance that may underlie differential clinical outcomes of therapy sequence and combination.
 
Overall design Gene expression profiles of 41 samples after progression on Immune Checkpoint Blockade treatment, generated by RNAseq.

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Authors state that due to Swedish and Danish laws, the patient consent, and the risk that the sequencing data contains personally-identifiable information and hereditary mutations, we cannot deposit the short sequencing read data in a public access repository
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Contributor(s) Lauss M, Jönsson G, Harbst K
Citation(s) 38594286
Submission date Oct 10, 2023
Last update date Apr 24, 2024
Contact name Martin Lauss
Organization name Lund University
Department Dept of Oncology
Street address Barngatan 2B
City Lund
ZIP/Postal code 22185
Country Sweden
 
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (41)
GSM7833076 Pat5
GSM7833077 Pat6
GSM7833078 Pat8
This SubSeries is part of SuperSeries:
GSE244984 Molecular patterns of resistance to immune checkpoint blockade in melanoma
Relations
BioProject PRJNA1026569

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
GSE244982_ProcessedData_bulkRNAseq.txt.gz 1.7 Mb (ftp)(http) TXT
Raw data not provided for this record

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