骨髓微环境中协调的免疫细胞网络定义了过继细胞疗法中的移植物抗白血病反应

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.