Dhodapkar Madhav V, Dhodapkar Kavita M
Departments of Internal Medicine (Hematology); Immunobiology, Yale University, New Haven, CT; Yale Cancer Center, Yale University, New Haven, CT.
Pediatrics (Hematology-Oncology); Yale Cancer Center, Yale University, New Haven, CT.
Semin Oncol. 2015 Aug;42(4):617-25. doi: 10.1053/j.seminoncol.2015.05.009. Epub 2015 Jun 3.
The therapeutic potential of the immune system in the context of hematologic malignancies has long been appreciated particularly due to the curative impact of allogeneic hematopoietic stem cell transplantation (SCT). The role of immune system in shaping the biology and evolution of these tumors is now well recognized. While the contribution of the immune system in anti-tumor effects of certain therapies such as immune-modulatory drugs and monoclonal antibodies active in hematologic malignancies is quite evident, the immune system has also been implicated in anti-tumor effects of other targeted therapies. The horizon of immune-based therapies in hematologic malignancies is rapidly expanding with promising results from immune-modulatory drugs, immune-checkpoint blockade, and adoptive cellular therapies, including genetically-modified T cells. Hematologic malignancies present distinct issues (relative to solid tumors) for the application of immune therapies due to differences in cell of origin/developmental niche of tumor cells, and patterns of involvement such as common systemic involvement of secondary lymphoid tissues. This article discusses the rapidly changing landscape of immune modulation in hematologic malignancies and emphasizes areas wherein hematologic malignancies present distinct opportunities for immunologic approaches to prevent or treat cancer.
长期以来,免疫系统在血液系统恶性肿瘤治疗方面的潜力一直备受关注,尤其是异基因造血干细胞移植(SCT)的治愈效果。免疫系统在塑造这些肿瘤的生物学特性和演变过程中的作用现已得到充分认识。虽然免疫系统在某些疗法(如对血液系统恶性肿瘤有效的免疫调节药物和单克隆抗体)的抗肿瘤效应中的贡献相当明显,但免疫系统也与其他靶向疗法的抗肿瘤效应有关。随着免疫调节药物、免疫检查点阻断以及过继性细胞疗法(包括基因改造的T细胞)取得了令人鼓舞的成果,血液系统恶性肿瘤基于免疫的治疗前景正在迅速拓展。由于肿瘤细胞的起源/发育微环境以及受累模式(如继发性淋巴组织常见的全身受累)存在差异,血液系统恶性肿瘤(相对于实体瘤)在免疫治疗的应用方面存在独特的问题。本文讨论了血液系统恶性肿瘤中免疫调节迅速变化的形势,并强调了血液系统恶性肿瘤在免疫方法预防或治疗癌症方面存在独特机会的领域。