High percentage of bone marrow CD8+ tissue-resident-like T cells predicts inferior survival in patients with acute myeloid leukemia

Background Acute myeloid leukemia (AML) is a malignant clonal blood disease and the most common type of acute leukemia in adults. Despite continuous advances in treatments, the long-term prognosis of AML has not improved substantially. Tissue-resident memory T cells (TRMs) infiltrating solid tumors could influence tumor progression and the response to immune therapies; however, the proportion and prognostic significance of TRMs in the bone marrow (BM) of patients with AML are unclear. Methods We use flow cytometry to assay the phenotypic of 49 BM samples from patients newly diagnosed with AML (ND-AML). The Kaplan–Meier Plotter database verified the relationship between the expression of CD8 ⁺ TRM-like T cell characteristic genes (CD8A, CD69, and TOX) and patient survival. Additionally, to further explored the existence and function of TRM-like CD8 ⁺ T cells in the BM by analyzing the single cell proteo-genomic dataset of BM from AML and healthy. Results We found that the BM CD8 ⁺ effector memory (TEM) cells highly expressed CD69 (CD8 ⁺ TRM-like T cells), and their number significantly increased in ND-AML compared with that in HIs. The high CD8 ⁺ TRM-like subset is associated with poor overall survival. The Kaplan–Meier Plotter database verified that the survival rate of patients with high expression of CD8 ⁺ TRM-like T cell characteristic genes was significantly reduced, especially in the M4 and M5 subtypes. Phenotypic analysis revealed that the BM CD8 ⁺ TRM-like subpopulation exhibited exhausted T cell characteristics, but its high expression of CD27 and CD28 and low expression of CD57 suggest its high proliferative potential. The single-cell proteogenomic dataset confirmed the existence of TRM-like CD8 ⁺ T cells in the BM of AML and verified the high expression of immune checkpoints and costimulatory molecules. Conclusions We found that the accumulation of BM CD8 ⁺ TRM-like subset could be considered as an immune related survival prediction marker for patients with AML. Although the mechanisms of BM CD8 ⁺ TRM-like subset in driving immune escape in AML remains unknown, we believe that the targeted reversal of the function of this subset through immune checkpoint inhibitors and another immune-related “brake” may benefit the survival of some patients with AML.