Katie Maurer, Cameron Y Park, Shouvik Mani, Mehdi Borji, Livius Penter, Yinuo Jin, Jia Yi Zhang, Crystal Shin, James R Brenner, Jackson Southard, Sachi Krishna, Wesley Lu, Haoxiang Lyu, Domenic Abbondanza, Chanell Mangum, Lars Rønn Olsen, Donna S Neuberg, Pavan Bachireddy, Samouil L Farhi, Shuqiang Li, Kenneth J Livak, Jerome Ritz, Robert J Soiffer, Catherine J Wu, Elham Azizi
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...
February 12, 2024: bioRxiv