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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 26, 2024 |
| Title |
NK cell cytotoxicity shapes the clonal evolution of B cell leukemia [ATAC-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| 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.
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| 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.
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| 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 |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Sep 25, 2024 |
| Last update date |
Nov 27, 2024 |
| Contact name |
Aleksandr Bykov |
| E-mail(s) |
[email protected]
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| Organization name |
CCRI
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| Department |
BiCU
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| Street address |
Zimmermannpl. 10
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| City |
Vienna |
| ZIP/Postal code |
1090 |
| Country |
Austria |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (125)
|
| GSM8537413 |
Tumor_only, Cell_line_A, timepoint_1, EXP_9.5, rep_1 |
| GSM8537414 |
Tumor_only, Cell_line_A, timepoint_1, EXP_9.5, rep_2 |
| GSM8537415 |
Tumor_only, Cell_line_A, timepoint_1, EXP_9.5, rep_3 |
| GSM8537416 |
Tumor_only, Cell_line_B, timepoint_1, EXP_9.5, rep_1 |
| GSM8537417 |
Tumor_only, Cell_line_B, timepoint_1, EXP_9.5, rep_2 |
| GSM8537418 |
Tumor_only, Cell_line_B, timepoint_1, EXP_9.5, rep_3 |
| GSM8537419 |
Tumor_only, Cell_line_C, timepoint_1, EXP_9.5, rep_1 |
| GSM8537420 |
Tumor_only, Cell_line_C, timepoint_1, EXP_9.5, rep_2 |
| GSM8537421 |
Tumor_only, Cell_line_C, timepoint_1, EXP_9.5, rep_3 |
| GSM8537422 |
Tumor_only, Cell_line_D, timepoint_1, EXP_9.5, rep_1 |
| GSM8537423 |
Tumor_only, Cell_line_D, timepoint_1, EXP_9.5, rep_2 |
| GSM8537424 |
Tumor_only, Cell_line_D, timepoint_1, EXP_9.5, rep_3 |
| GSM8537425 |
Tumor_plus_NK, Cell_line_A, timepoint_1, EXP_9.5, rep_1 |
| GSM8537426 |
Tumor_plus_NK, Cell_line_A, timepoint_1, EXP_9.5, rep_2 |
| GSM8537427 |
Tumor_plus_NK, Cell_line_A, timepoint_1, EXP_9.5, rep_3 |
| GSM8537428 |
Tumor_plus_NK, Cell_line_B, timepoint_1, EXP_9.5, rep_1 |
| GSM8537429 |
Tumor_plus_NK, Cell_line_B, timepoint_1, EXP_9.5, rep_2 |
| GSM8537430 |
Tumor_plus_NK, Cell_line_B, timepoint_1, EXP_9.5, rep_3 |
| GSM8537431 |
Tumor_plus_NK, Cell_line_C, timepoint_1, EXP_9.5, rep_1 |
| GSM8537432 |
Tumor_plus_NK, Cell_line_C, timepoint_1, EXP_9.5, rep_2 |
| GSM8537433 |
Tumor_plus_NK, Cell_line_C, timepoint_1, EXP_9.5, rep_3 |
| GSM8537434 |
Tumor_plus_NK, Cell_line_D, timepoint_1, EXP_9.5, rep_1 |
| GSM8537435 |
Tumor_plus_NK, Cell_line_D, timepoint_1, EXP_9.5, rep_2 |
| GSM8537436 |
Tumor_plus_NK, Cell_line_D, timepoint_1, EXP_9.5, rep_3 |
| GSM8537437 |
Tumor_plus_NK, Cell_line_A, timepoint_2, EXP_9.5, rep_1 |
| GSM8537438 |
Tumor_plus_NK, Cell_line_A, timepoint_2, EXP_9.5, rep_2 |
| GSM8537439 |
Tumor_plus_NK, Cell_line_A, timepoint_2, EXP_9.5, rep_3 |
| GSM8537440 |
Tumor_plus_NK, Cell_line_B, timepoint_2, EXP_9.5, rep_1 |
| GSM8537441 |
Tumor_plus_NK, Cell_line_B, timepoint_2, EXP_9.5, rep_2 |
| GSM8537442 |
Tumor_plus_NK, Cell_line_B, timepoint_2, EXP_9.5, rep_3 |
| GSM8537443 |
Tumor_plus_NK, Cell_line_C, timepoint_2, EXP_9.5, rep_1 |
| GSM8537444 |
Tumor_plus_NK, Cell_line_C, timepoint_2, EXP_9.5, rep_2 |
| GSM8537445 |
Tumor_plus_NK, Cell_line_C, timepoint_2, EXP_9.5, rep_3 |
| GSM8537446 |
Tumor_plus_NK, Cell_line_D, timepoint_2, EXP_9.5, rep_1 |
| GSM8537447 |
Tumor_plus_NK, Cell_line_D, timepoint_2, EXP_9.5, rep_2 |
| GSM8537448 |
Tumor_plus_NK, Cell_line_D, timepoint_2, EXP_9.5, rep_3 |
| GSM8537449 |
Tumor_only, Cell_line_C, timepoint_1, EXP_9.5.1, rep_1 |
| GSM8537450 |
Tumor_only, Cell_line_C, timepoint_1, EXP_9.5.1, rep_2 |
| GSM8537451 |
Tumor_only, Cell_line_C, timepoint_1, EXP_9.5.1, rep_3 |
| GSM8537452 |
Tumor_plus_NK, Cell_line_C, timepoint_1, EXP_9.5.1, rep_1 |
| GSM8537453 |
Tumor_plus_NK, Cell_line_C, timepoint_1, EXP_9.5.1, rep_2 |
| GSM8537454 |
Tumor_plus_NK, Cell_line_C, timepoint_1, EXP_9.5.1, rep_3 |
| GSM8537455 |
Tumor_plus_NK, Cell_line_C, timepoint_2, EXP_9.5.1, rep_1 |
| GSM8537456 |
Tumor_plus_NK, Cell_line_C, timepoint_2, EXP_9.5.1, rep_2 |
| GSM8537457 |
Tumor_plus_NK, Cell_line_C, timepoint_2, EXP_9.5.1, rep_3 |
| GSM8537458 |
Tumor_only, Cell_line_A, timepoint_1, EXP_9.6, rep_1 |
| GSM8537459 |
Tumor_only, Cell_line_A, timepoint_1, EXP_9.6, rep_2 |
| GSM8537460 |
Tumor_only, Cell_line_A, timepoint_1, EXP_9.6, rep_3 |
| GSM8537461 |
Tumor_only, Cell_line_B, timepoint_1, EXP_9.6, rep_1 |
| GSM8537462 |
Tumor_only, Cell_line_B, timepoint_1, EXP_9.6, rep_2 |
| GSM8537463 |
Tumor_only, Cell_line_B, timepoint_1, EXP_9.6, rep_3 |
| GSM8537464 |
Tumor_only, Cell_line_C, timepoint_1, EXP_9.6, rep_1 |
| GSM8537465 |
Tumor_only, Cell_line_C, timepoint_1, EXP_9.6, rep_2 |
| GSM8537466 |
Tumor_only, Cell_line_C, timepoint_1, EXP_9.6, rep_3 |
| GSM8537467 |
Tumor_only, Cell_line_D, timepoint_1, EXP_9.6, rep_1 |
| GSM8537468 |
Tumor_only, Cell_line_D, timepoint_1, EXP_9.6, rep_2 |
| GSM8537469 |
Tumor_only, Cell_line_D, timepoint_1, EXP_9.6, rep_3 |
| GSM8537470 |
Tumor_plus_NK, Cell_line_A, timepoint_1, EXP_9.6, rep_1 |
| GSM8537471 |
Tumor_plus_NK, Cell_line_A, timepoint_1, EXP_9.6, rep_2 |
| GSM8537472 |
Tumor_plus_NK, Cell_line_A, timepoint_1, EXP_9.6, rep_3 |
| GSM8537473 |
Tumor_plus_NK, Cell_line_B, timepoint_1, EXP_9.6, rep_1 |
| GSM8537474 |
Tumor_plus_NK, Cell_line_B, timepoint_1, EXP_9.6, rep_2 |
| GSM8537475 |
Tumor_plus_NK, Cell_line_B, timepoint_1, EXP_9.6, rep_3 |
| GSM8537476 |
Tumor_plus_NK, Cell_line_C, timepoint_1, EXP_9.6, rep_1 |
| GSM8537477 |
Tumor_plus_NK, Cell_line_C, timepoint_1, EXP_9.6, rep_2 |
| GSM8537478 |
Tumor_plus_NK, Cell_line_C, timepoint_1, EXP_9.6, rep_3 |
| GSM8537479 |
Tumor_plus_NK, Cell_line_D, timepoint_1, EXP_9.6, rep_1 |
| GSM8537480 |
Tumor_plus_NK, Cell_line_D, timepoint_1, EXP_9.6, rep_2 |
| GSM8537481 |
Tumor_plus_NK, Cell_line_D, timepoint_1, EXP_9.6, rep_3 |
| GSM8537482 |
Tumor_plus_NK, Cell_line_A, timepoint_2, EXP_9.6, rep_1 |
| GSM8537483 |
Tumor_plus_NK, Cell_line_A, timepoint_2, EXP_9.6, rep_2 |
| GSM8537484 |
Tumor_plus_NK, Cell_line_A, timepoint_2, EXP_9.6, rep_3 |
| GSM8537485 |
Tumor_plus_NK, Cell_line_B, timepoint_2, EXP_9.6, rep_1 |
| GSM8537486 |
Tumor_plus_NK, Cell_line_B, timepoint_2, EXP_9.6, rep_2 |
| GSM8537487 |
Tumor_plus_NK, Cell_line_B, timepoint_2, EXP_9.6, rep_3 |
| GSM8537488 |
Tumor_plus_NK, Cell_line_C, timepoint_2, EXP_9.6, rep_1 |
| GSM8537489 |
Tumor_plus_NK, Cell_line_C, timepoint_2, EXP_9.6, rep_2 |
| GSM8537490 |
Tumor_plus_NK, Cell_line_C, timepoint_2, EXP_9.6, rep_3 |
| GSM8537491 |
Tumor_plus_NK, Cell_line_D, timepoint_2, EXP_9.6, rep_1 |
| GSM8537492 |
Tumor_plus_NK, Cell_line_D, timepoint_2, EXP_9.6, rep_2 |
| GSM8537493 |
Tumor_plus_NK, Cell_line_D, timepoint_2, EXP_9.6, rep_3 |
| GSM8537494 |
Tumor_only, Cell_line_D, timepoint_1, EXP_9.6.1, rep_1 |
| GSM8537495 |
Tumor_only, Cell_line_D, timepoint_1, EXP_9.6.1, rep_2 |
| GSM8537496 |
Tumor_plus_NK, Cell_line_D, timepoint_1, EXP_9.6.1, rep_1 |
| GSM8537497 |
Tumor_plus_NK, Cell_line_D, timepoint_1, EXP_9.6.1, rep_2 |
| GSM8537498 |
Tumor_plus_NK, Cell_line_D, timepoint_1, EXP_9.6.1, rep_3 |
| GSM8537499 |
Tumor_plus_NK, Cell_line_D, timepoint_2, EXP_9.6.1, rep_1 |
| GSM8537500 |
Tumor_plus_NK, Cell_line_D, timepoint_2, EXP_9.6.1, rep_2 |
| GSM8537501 |
Tumor_plus_NK, Cell_line_D, timepoint_2, EXP_9.6.1, rep_3 |
| GSM8537502 |
Tumor_only, Cell_line_A, timepoint_1, EXP_9.7, rep_1 |
| GSM8537503 |
Tumor_only, Cell_line_A, timepoint_1, EXP_9.7, rep_2 |
| GSM8537504 |
Tumor_only, Cell_line_A, timepoint_1, EXP_9.7, rep_3 |
| GSM8537505 |
Tumor_only, Cell_line_B, timepoint_1, EXP_9.7, rep_1 |
| GSM8537506 |
Tumor_only, Cell_line_B, timepoint_1, EXP_9.7, rep_2 |
| GSM8537507 |
Tumor_only, Cell_line_B, timepoint_1, EXP_9.7, rep_3 |
| GSM8537508 |
Tumor_only, Cell_line_C, timepoint_1, EXP_9.7, rep_1 |
| GSM8537509 |
Tumor_only, Cell_line_C, timepoint_1, EXP_9.7, rep_2 |
| GSM8537510 |
Tumor_only, Cell_line_C, timepoint_1, EXP_9.7, rep_3 |
| GSM8537511 |
Tumor_only, Cell_line_D, timepoint_1, EXP_9.7, rep_1 |
| GSM8537512 |
Tumor_only, Cell_line_D, timepoint_1, EXP_9.7, rep_2 |
| GSM8537513 |
Tumor_only, Cell_line_D, timepoint_1, EXP_9.7, rep_3 |
| GSM8537514 |
Tumor_plus_NK, Cell_line_A, timepoint_1, EXP_9.7, rep_1 |
| GSM8537515 |
Tumor_plus_NK, Cell_line_A, timepoint_1, EXP_9.7, rep_2 |
| GSM8537516 |
Tumor_plus_NK, Cell_line_A, timepoint_1, EXP_9.7, rep_3 |
| GSM8537517 |
Tumor_plus_NK, Cell_line_B, timepoint_1, EXP_9.7, rep_1 |
| GSM8537518 |
Tumor_plus_NK, Cell_line_B, timepoint_1, EXP_9.7, rep_2 |
| GSM8537519 |
Tumor_plus_NK, Cell_line_B, timepoint_1, EXP_9.7, rep_3 |
| GSM8537520 |
Tumor_plus_NK, Cell_line_C, timepoint_1, EXP_9.7, rep_1 |
| GSM8537522 |
Tumor_plus_NK, Cell_line_C, timepoint_1, EXP_9.7, rep_2 |
| GSM8537523 |
Tumor_plus_NK, Cell_line_C, timepoint_1, EXP_9.7, rep_3 |
| GSM8537525 |
Tumor_plus_NK, Cell_line_D, timepoint_1, EXP_9.7, rep_1 |
| GSM8537527 |
Tumor_plus_NK, Cell_line_D, timepoint_1, EXP_9.7, rep_2 |
| GSM8537529 |
Tumor_plus_NK, Cell_line_D, timepoint_1, EXP_9.7, rep_3 |
| GSM8537530 |
Tumor_plus_NK, Cell_line_A, timepoint_2, EXP_9.7, rep_1 |
| GSM8537531 |
Tumor_plus_NK, Cell_line_A, timepoint_2, EXP_9.7, rep_2 |
| GSM8537532 |
Tumor_plus_NK, Cell_line_A, timepoint_2, EXP_9.7, rep_3 |
| GSM8537533 |
Tumor_plus_NK, Cell_line_B, timepoint_2, EXP_9.7, rep_1 |
| GSM8537534 |
Tumor_plus_NK, Cell_line_B, timepoint_2, EXP_9.7, rep_2 |
| GSM8537535 |
Tumor_plus_NK, Cell_line_B, timepoint_2, EXP_9.7, rep_3 |
| GSM8537536 |
Tumor_plus_NK, Cell_line_C, timepoint_2, EXP_9.7, rep_1 |
| GSM8537537 |
Tumor_plus_NK, Cell_line_C, timepoint_2, EXP_9.7, rep_2 |
| GSM8537538 |
Tumor_plus_NK, Cell_line_C, timepoint_2, EXP_9.7, rep_3 |
| GSM8537539 |
Tumor_plus_NK, Cell_line_D, timepoint_2, EXP_9.7, rep_1 |
| GSM8537540 |
Tumor_plus_NK, Cell_line_D, timepoint_2, EXP_9.7, rep_2 |
| GSM8537541 |
Tumor_plus_NK, Cell_line_D, timepoint_2, EXP_9.7, rep_3 |
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| Relations |
| BioProject |
PRJNA1165217 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE278010_RAW.tar |
143.3 Mb |
(http)(custom) |
TAR (of BROADPEAK) |
| GSE278010_consensus_peaks.mLb.clN.featureCounts.txt.gz |
29.7 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
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