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Molecular portraits of tumor mutational and micro-environmental sculpting by immune checkpoint blockade therapy

UID: 10509

Author(s): Riaz, Nadeem*, Havel, Jonathan J.*, Makarov, Vladimir*, Desrichard, Alexis*, Chan, Timothy A.* * MSK affiliated

Description
Summary from the GEO: "Immune checkpoint blockade (ICB) has demonstrated significant promise for the treatment of advanced malignancies. Anti-CTLA4 and ant-PD1 therapy can activate the immune system and result in durable control in diseases such as melanoma and non-small cell lung cancer.
109 RNASeq samples (58 On-treatment and 51 Pre-treatment) from 65 patients."

Abstract from the publication that further explains the dataset: "The mechanisms by which immune checkpoint blockade modulates tumor evolution during therapy are unclear. We assessed genomic changes in tumors from 68 patients with advanced melanoma, who progressed on ipilimumab or were ipilimumab-naive, before and after nivolumab initiation (CA209-038 study). Tumors were analyzed by whole-exome, transcriptome, and/or T cell receptor (TCR) sequencing. In responding patients, mutation and neoantigen load were reduced from baseline, and analysis of intratumoral heterogeneity during therapy demonstrated differential clonal evolution within tumors and putative selection against neoantigenic mutations on-therapy. Transcriptome analyses before and during nivolumab therapy revealed increases in distinct immune cell subsets, activation of specific transcriptional networks, and upregulation of immune checkpoint genes that were more pronounced in patients with response. Temporal changes in intratumoral TCR repertoire revealed expansion of T cell clones in the setting of neoantigen loss. Comprehensive genomic profiling data in this study provide insight into nivolumab's mechanism of action. Mutation burden decreases with successful checkpoint blockade therapy in patients with melanoma, suggesting that selection against mutant neoepitopes may be a critical mechanism of action of Nivolumab."
Subject of Study
Homo sapiens
Subject(s)
Carcinoma, Non-Small-Cell Lung
Immunotherapy
Melanoma
OncoTree Cancer Type(s)
Melanoma
Non-Small Cell Lung Cancer
Access via GEO

Raw, FPKM, and RLD sequencing (CSV) and plain text cytolytic score data
Accession #: GSE91061

Access via SRA

RNA Sequence reads for 109 samples.
Accession #: SRP094781

Access via BioProject

Additional information about overall initiative.
Accession #: PRJNA356761

Access Restrictions
Free to All
Access Instructions
The NCBI Gene Expression Omnibus, SRA, and BioProject databases provide open access to these files.
Associated Publications
Campesato L, Budhu S, Tchaicha J, et al. Blockade of the AHR restricts a Treg-macrophage suppressive axis induced by L-Kynurenine. Nature Communications. 2020; 11:4011.
Riaz N, Havel J, Makarov V, et al. Tumor and microenvironment evolution during immunotherapy with nivolumab. Cell. 2017; 171(4):934-949.e15.
Data Type
Genomic
Equipment Used
Illumina Genome Analyzer
Dataset Format(s)
CSV, Plain Text, SRA, gzip
Dataset Size
15.6 MB (FPKM), 3.4 MB (raw), 18.4 MB (RLD), 1.8 KB (TXT), SRA broken up into files of 2-3GB
Data Catalog Record Updated
2023-12-07