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| Status |
Public on Jan 24, 2025 |
| Title |
Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Understanding how intra-tumoral immune populations coordinate to generate anti-tumor responses following therapy can guide precise treatment prioritization. We performed systematic dissection of an established adoptive cellular therapy, donor lymphocyte infusion (DLI) by analyzing 348,905 single-cell transcriptomes from 74 longitudinal bone-marrow samples of 25 patients with relapsed myeloid leukemia; with a subset evaluated by protein-based spatial analysis. In acute myelogenous leukemia (AML) responders, diverse immune cell types within the bone-marrow microenvironment (BME) were predicted to interact with a clonally expanded population of ZNF683+GZMB+ CD8+ cytotoxic T lymphocytes (CTLs) which demonstrated in vitro specificity for autologous leukemia. This population, originating predominantly from the DLI product, expanded concurrently with NK and B cells. AML nonresponder BME revealed a paucity of crosstalk and elevated TIGIT expression in CD8+ CTLs. Our study highlights recipient BME differences as a key determinant of effective anti-leukemia response and opens new opportunities to modulate cell-based leukemia-directed therapy.
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| Overall design |
single-cell RNA sequencing and CITE protein sequencing from 9 AML patients and 16 CML patients, with mutliple time points before and after relapse and treatment with donor lymphocyte infusion
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Submitter states that missing raw data are being made available for controlled access in dbGaP.
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| Contributor(s) |
Maurer K, Park CY, Mani S, Borji M, Raths F, Gouin III KH, Penter L, Jin Y, Zhang JY, Shin C, Brenner JR, Southard J, Krishna S, Lu W, Lyu H, Abbondanza D, Magnum C, Olsen LR, Lawson MJ, Fabani M, Neuberg DS, Bachireddy P, Glezer EN, Farhi SL, Li S, Livak KJ, Ritz J, Soiffer RJ, Wu CJ, Azizi E |
| Citation(s) |
39854478 |
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| Submission date |
Feb 10, 2024 |
| Last update date |
Jan 29, 2025 |
| Contact name |
Cameron Park |
| E-mail(s) |
cyp2111@columbia.edu
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| Organization name |
Columbia University
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| Street address |
500 W 120th St
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10011 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (132)
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| Relations |
| BioProject |
PRJNA1075299 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE255530_cite_data.csv.gz |
11.7 Mb |
(ftp)(http) |
CSV |
| GSE255530_counts_data.csv.gz |
1.0 Gb |
(ftp)(http) |
CSV |
| Raw data not provided for this record |
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