Bulk RNA sequencing reveals the comprehensive genetic characteristics of human cord blood-derived natural killer cells

批量 RNA 测序揭示人类脐带血来源的自然杀伤细胞的全面遗传特征

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作者:Takayuki Morimoto, Tsutomu Nakazawa, Ryosuke Maeoka, Ryosuke Matsuda, Mitsutoshi Nakamura, Fumihiko Nishimura, Shuichi Yamada, Ichiro Nakagawa, Young-Soo Park, Takahiro Tsujimura

Conclusions

We demonstrated the characteristics of human CBNKCs. Cell-based therapy using the CBNKCs is promising for treating GBM.

Methods

Frozen T cell-free CB mononuclear cells were cultured with recombinant human interleukin (rhIL)-18 and rhIL-2 in anti-NKp46 and anti-CD16 antibody immobilization settings. After 14-day expansion, the total RNA of the CBNKCs or PBNKCs was extracted and transcriptomic analyses was performed to determine their similarities and differences. We also examined CBNKC and PBNKC activity against a GBM cell line.

Results

Differential expression gene analysis revealed that some NK activating and inhibitory receptors were significantly downregulated in the CBNKCs compared to PBNKCs. Furthermore, genes related to anti-apoptosis and proliferation were upregulated in the CBNKCs. Enrichment analysis determined that the gene sets related to immune response and cytokines were enriched in the CBNKCs. Gene set enrichment analysis demonstrated that the immune response pathway was upregulated in the CBNKCs. Cytotoxic assays using impedance-based cell analyzer revealed that the CBNKCs enhanced NKC-mediated cytotoxicity on GBM cells as compared to the PBNKCs. Conclusions: We demonstrated the characteristics of human CBNKCs. Cell-based therapy using the CBNKCs is promising for treating GBM.

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