Abstract
Acute myeloid leukemia (AML) is an aggressive hematologic cancer characterized by poor
clinical outcomes. Despite advancements in therapeutic approaches, such as the combination
of venetoclax, FLT3 inhibitors, or IDH1/2 inhibitors with traditional chemotherapy, many
patients relapse, urging the need for improved treatment strategies. Emerging data suggest
that immunotherapies could represent a promising option for AML treatment. In this study,
we aimed to determine whether AML patients exhibit tumor-specific T cell responses. We
characterized T cells from paired blood (PBMC) and bone marrow (BM) samples using mass
cytometry and TCR sequencing. Through this approach, we identified a distinct population of
CD8+ T cells specific to the bone marrow (CD69+, PD-1+) indicating an activated state with a
unique transcriptional and cytokine profile. Additionally, we highlighted a non-specific
population resulting from blood contamination. TCR sequencing revealed clonal expansion
within this bone marrow-specific population, indicating antigen-driven activation. Finally, we
analyzed antigenic specificity using MHC-I tetramer screening in these patients. In conclusion,
these findings provide a deeper understanding of the immune landscape in AML both
phenotypically and functionally, and pave the way for further studies aimed at developing
targeted immunotherapy strategies.