Immunobiology · 2025
Kasumi-1 exosome plays a major T-cell immune evasion role in TP53-type acute leukemia.
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Du Yunyun, Fan Zhenfeng, Li Lijiao, Xue Yong, Zhao Shixiang
Аннотация
BACKGROUND: The treatment and prognosis for TP53-mutant acute leukemia (AL) are notably unfavorable. Tumor-derived exosomes are participating in tumorigenesis and immunomodulation. Our objective was to characterize the exosome-mediated immune landscape in TP53-mutant AL.
METHODS: Four TP53 AL cell lines were selected for study. RT-qPCR and western blot were used to determine the PD-L1 and TP53. AL exosomes (AL-exos) were co-cultured with PBMC. Flow cytometry was used to determine immune cell and PD-1 expression. Transmission electron microscopy and western blot determination of MOLM-13 and Kasumi-1 exosome surface markers HSP70, CD9, CD63, and CD81. Subsequently, miRNA sequencing was performed.
RESULTS: In TP53 AL cell lines, PD-L1 protein, and mRNA expression increased sequentially in MOLM-13, Kasumi-1, Molt-4, and KG-1 cells. Notably, MOLM-13 and Kasumi-1 exhibited the highest TP53 expression. Flow cytometry results indicated that Kasumi-1-exosomes had a more pronounced effect on immune cells, resulting in a significant reduction in CD8+ T cell populations and a notable increase in Tregs. Notably, its PD-1 expression was significantly elevated. miRNA analysis showed that the DEGs were primarily enriched in signaling transduction and endocytosis pathways.
CONCLUSION: Kasumi-1-exos promote DNA damage and PD-L1 enrichment through clathrin-mediated plasma membrane fusion, which ultimately leads to AL immune escape characterized primarily by decreased CD8+ T cell expression and increased Treg expression.
METHODS: Four TP53 AL cell lines were selected for study. RT-qPCR and western blot were used to determine the PD-L1 and TP53. AL exosomes (AL-exos) were co-cultured with PBMC. Flow cytometry was used to determine immune cell and PD-1 expression. Transmission electron microscopy and western blot determination of MOLM-13 and Kasumi-1 exosome surface markers HSP70, CD9, CD63, and CD81. Subsequently, miRNA sequencing was performed.
RESULTS: In TP53 AL cell lines, PD-L1 protein, and mRNA expression increased sequentially in MOLM-13, Kasumi-1, Molt-4, and KG-1 cells. Notably, MOLM-13 and Kasumi-1 exhibited the highest TP53 expression. Flow cytometry results indicated that Kasumi-1-exosomes had a more pronounced effect on immune cells, resulting in a significant reduction in CD8+ T cell populations and a notable increase in Tregs. Notably, its PD-1 expression was significantly elevated. miRNA analysis showed that the DEGs were primarily enriched in signaling transduction and endocytosis pathways.
CONCLUSION: Kasumi-1-exos promote DNA damage and PD-L1 enrichment through clathrin-mediated plasma membrane fusion, which ultimately leads to AL immune escape characterized primarily by decreased CD8+ T cell expression and increased Treg expression.