Adair Jennifer E, Kubek Sara P, Kiem Hans-Peter
Stem Cell and Gene Therapy Program, Fred Hutchison Cancer Research Center, 1100 Fairview Avenue N. D1-100 Seattle, WA 98109-1024, USA.
Stem Cell and Gene Therapy Program, Fred Hutchison Cancer Research Center, 1100 Fairview Avenue N. D1-100 Seattle, WA 98109-1024, USA.
Hematol Oncol Clin North Am. 2017 Oct;31(5):897-912. doi: 10.1016/j.hoc.2017.06.012.
Hematopoietic stem cells (HSCs) are unique in their ability to self-renew and generate all blood lineages for the entire life. HSC modification affects red blood cells, platelets, lymphocytes, and myeloid cells. Chemotherapy can result in myelosuppression, limiting effective chemotherapy administration. For diseases like glioblastoma, high expression of methlylguanine methyltransferase can inactivate alkylating agent chemotherapy. Here we discuss how HSCs can be modified to overcome this resistance, permitting sensitization of tumors to chemotherapy while simultaneously protecting the hematopoietic system. We also discuss how HSCs can be harnessed to produce powerful tumor killing T cells, potentially benefitting and complementing T-cell-based immunotherapies.
造血干细胞（HSCs）具有自我更新以及在整个生命周期内产生所有血细胞谱系的独特能力。造血干细胞的修饰会影响红细胞、血小板、淋巴细胞和髓系细胞。化疗可导致骨髓抑制，限制有效化疗药物的施用。对于胶质母细胞瘤等疾病，甲基鸟嘌呤甲基转移酶的高表达可使烷化剂化疗失活。在此，我们讨论如何修饰造血干细胞以克服这种耐药性，使肿瘤对化疗敏感，同时保护造血系统。我们还讨论了如何利用造血干细胞产生强大的肿瘤杀伤性T细胞，这可能有益于并补充基于T细胞的免疫疗法。
