Based on cell markers identified through in vivo scRNA-seq data, TARGET-ALL-P2 datasets, and integrated machine learning algorithms, ssGSEA was employed to identify key cells with prognostic value and simulate adoptive cell transfer therapy (ACT), and the study demonstrated that using CXCR6+CD4+T cells to mimic ACT therapy could reshape the bone marrow microenvironment to achieve anti-tumor effects, with CXCR6 not being a marker of resident memory CD4+T cells based on the expression of genes involved in their formation. Here, CXCR6 is linked to acute lymphoblastic leukemia.