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Series GSE278006 Query DataSets for GSE278006
Status Public on Nov 26, 2024
Title NK cell cytotoxicity shapes the clonal evolution of B cell leukemia [RNA-seq]
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary The term cancer immunoediting describes the dual role by which the immune system can suppress and promote tumour growth and is divided into three phases: elimination, equilibrium and escape. The role of NK cells has mainly been attributed to the elimination phase. Here we show that NK cells play a role in all three phases of cancer immunoediting. Extended co-culturing of DNA barcoded mouse BCR/ABLp185+ B acute lymphoblastic leukaemia cells with NK cells allowed for a quantitative measure of NK cell-mediated immunoediting. Whereas most tumour cell clones were efficiently eliminated by NK cells, a certain fraction of tumour cells harboured an intrinsic primary resistance. Furthermore, DNA barcoding revealed tumour cell clones with secondary resistance, which stochastically acquired resistance to NK cells. NK cell cytotoxicity put a selective pressure on B-ALL cells inducing primary and secondary resistance, while resistant tumour cells were characterised by a full-blown IFN-g signature. Besides well-known regulators of immune evasion, our analysis of NK resistant tumour cells revealed the upregulation of novel genes, including Ly6a, which we found to drive NK cell resistance in leukaemic cells. We further translated our findings to the human system and showed that high LY6E expression on tumour cells impaired the physical interaction with NK cells and led to worse prognosis in leukaemia. Our results demonstrate that tumour cells are actively edited by NK cells during the equilibrium phase and use different avenues to escape NK cell-mediated eradication.
 
Overall design Experiment includes B-ALL alone and B-ALL cultured with WT, Ifng-/- and Prf-/- NK cells samples, which were anaylsed on different timepoints. Experiments was conducted in biological triplicates with 2 to 4 cell lines. Cell lines A: DNA barcoded tumour cell line 1. Originating from BCR/ABLp185+ cell line #13. B: DNA barcoded tumour cell line 2. Originating from BCR/ABLp185+ cell line #13. C: DNA barcoded tumour cell line 1. Originating from BCR/ABLp185+ cell line #15. D: DNA barcoded tumour cell line 2. Originating from BCR/ABLp185+ cell line #15. DNA barcode amplicons are sequenced in technical duplicates.
 
Contributor(s) Buri MC, Shoeb MR, Bykov A, Reiscak P, Baik H, Dupanovic A, David FO, Kovacic B, Hall-Glenn F, Dopa S, Urbauns J, Sippl L, Stofner S, Emminger D, Cosgrove J, Schinnerl D, Poetsch AR, Lehner M, Koenig X, PeriƩ L, Schumacher TN, Gotthardt D, Halbritter F, Putz EM
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Submission date Sep 25, 2024
Last update date Nov 27, 2024
Contact name Aleksandr Bykov
E-mail(s) [email protected]
Organization name CCRI
Department BiCU
Street address Zimmermannpl. 10
City Vienna
ZIP/Postal code 1090
Country Austria
 
Platforms (3)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (241)
GSM8537158 Tumor_only, Cell_line_C, timepoint_1, EXP_9.4, rep_1
GSM8537159 Tumor_only, Cell_line_C, timepoint_1, EXP_9.4, rep_2
GSM8537160 Tumor_only, Cell_line_C, timepoint_1, EXP_9.4, rep_3
Relations
BioProject PRJNA1165216

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE278006_RAW.tar 228.8 Mb (http)(custom) TAR (of SF)
GSE278006_X01_X12_raw_counts.tsv.gz 1.6 Mb (ftp)(http) TSV
GSE278006_X19_X30_raw_counts.tsv.gz 2.0 Mb (ftp)(http) TSV
GSE278006_X31_X78_raw_counts.tsv.gz 2.1 Mb (ftp)(http) TSV
GSE278006_X85_X96_raw_counts.tsv.gz 2.0 Mb (ftp)(http) TSV
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Raw data are available in SRA

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