Coordinated Immune Cell Networks in the Bone Marrow Microenvironment Define the Graft versus Leukemia Response with Adoptive Cellular Therapy
Maurer, K.; Park, C.; Mani, S.; Borji, M.; Penter, L.; Jin, Y.; Zhang, J. Y.; Shin, C.; Brenner, J. R.; Southard, J.; Krishna, S.; Lu, W.; Lyu, H.; Abbondanza, D.; Mangum, C.; Olsen, L. R.; Neuberg, D. S.; Bachireddy, P.; Farhi, S. L.; Li, S.; Livak, K. J.; Ritz, J.; Soiffer, R. J.; Wu, C. J.; Azizi, E.
Show abstract
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; a subset was 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.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Ontogeny Dictates Oncogenic Potential, Lineage Hierarchy, and Therapy Response in Pediatric Leukemia 99%
- Leukemia cell of origin influences apoptotic priming and sensitivity to LSD1 inhibition 96%
- A novel type of monocytic leukemia stem cell revealed by the clinical use of venetoclax-based therapy 96%
Similar papers in this journal
- CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias 98%
- Disruption of a GATA2, TAL1, ERG regulatory circuit promotes erythroid transition in healthy and leukemic stem cells 97%
- Leukemia escapes immunity by imposing a Type-1 regulatory program on neoantigen-specific CD4+ T cells. 97%
Similar papers in this journal
Similar papers in this journal
- AML/T cell interactomics uncover correlates of patient outcomes and the key role of ICAM1 in T cell killing of AML 97%
- Spatial analysis reveals distinct immune phenotypes and tertiary lymphoid structure-like aggregates in pediatric acute myeloid leukemia 97%
- Identification of leukemia stem cell subsets with distinct transcriptional, epigenetic and functional properties 97%
Similar papers in this journal
- Single cell dissection of developmental origins and transcriptional heterogeneity in B-cell acute lymphoblastic leukemia 98%
- A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma 96%
- DUSP6 mediates resistance to JAK2 inhibition and drives leukemic progression 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.