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Series GSE278011 Query DataSets for GSE278011
Status Public on Nov 26, 2024
Title NK cell cytotoxicity shapes the clonal evolution of B cell leukemia [DNA barcoding]
Organism Mus musculus
Experiment type Other
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. 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, Perié L, Schumacher TN, Gotthardt D, Halbritter F, Putz EM
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Submission date Sep 25, 2024
Last update date Nov 26, 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 (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (298)
GSM8537542 3.13_EXP_9.6_C_Tumor+NK_timepoint 2_1_R1
GSM8537543 3.13_EXP_9.6_C_Tumor+NK_timepoint 2_1_R2
GSM8537544 3.13_EXP_9.6_C_Tumor+NK_timepoint 2_2_R1
Relations
BioProject PRJNA1165213

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Supplementary file Size Download File type/resource
GSE278011_valid_match_count_matrix_9.67811.xlsx 111.8 Mb (ftp)(http) XLSX
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Raw data are available in SRA
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