Sheikhi Abdolkarim, Jafarzadeh Abdollah
a Cellular And Molecular Immunology Research Laboratory, Department of Immunology , Dezful University of Medical Sciences , Dezful , Iran.
b Ontario Cancer Institute, University Health Network , Toronto , ON , Canada.
Hum Vaccin Immunother. 2017 Aug 3;13(8):1786-1788. doi: 10.1080/21645515.2017.1314874. Epub 2017 May 11.
Tumor cells escape from immune recognition by several mechanisms such as down-regulating of MHC class I molecules, losing of tumor antigens, etc. The purpose of cancer immunotherapy is to robust or reconstruct the capacity of the immune system to recognize and kill tumor cells by overwhelming the mechanisms by which tumors escape the immune response. One of the novel immunotherapeutic strategies were used to potentiate NK- and T cell functions is chimeric antigen receptor (CAR). CARs are composed of an antigen-binding domain of a molecule such as an antibody (that binds to a tumor associated antigens expressed on the surface of tumor cells) and an intracellular T cell activation domain. The CARs provide the recognition of target antigen in a MHC-independent manner. CAR-armed T cells may be unable to kill their targets in the absence of co-stimulators like NK cells. On the other hand, CAR-armed NK cells may also be unable to destroy their targets without receiving help signals from Th cells. Thus, if CAR-armed NK cells use together with CAR-armed T cells, NK cells will be aggregated to the tumor site. Thus, not only CAR T cells will obtain the necessary cytokines/costimulators from NK cells, but also other tumor specific T cells will be primed by recognition of tumor specific antigen (TSA) associated with MHC class I. These new specific primed T cells probably combat against tumor cells which have lost their TAAs that CAR-T cells are redirected to them.
肿瘤细胞通过多种机制逃避免疫识别，如下调MHC I类分子、丢失肿瘤抗原等。癌症免疫疗法的目的是通过克服肿瘤逃避免疫反应的机制，增强或重建免疫系统识别和杀死肿瘤细胞的能力。用于增强NK细胞和T细胞功能的一种新型免疫治疗策略是嵌合抗原受体（CAR）。CAR由诸如抗体（与肿瘤细胞表面表达的肿瘤相关抗原结合）等分子的抗原结合域和细胞内T细胞激活域组成。CAR以不依赖MHC的方式识别靶抗原。在没有像NK细胞这样的共刺激分子的情况下，携带CAR的T细胞可能无法杀死其靶标。另一方面，携带CAR的NK细胞在没有从Th细胞接收帮助信号的情况下也可能无法破坏其靶标。因此，如果携带CAR的NK细胞与携带CAR的T细胞一起使用，NK细胞将聚集到肿瘤部位。这样，不仅CAR T细胞将从NK细胞获得必要的细胞因子/共刺激分子，而且其他肿瘤特异性T细胞也将通过识别与MHC I类相关的肿瘤特异性抗原（TSA）而被激活。这些新的特异性激活的T细胞可能对抗那些已经丢失了CAR-T细胞被重定向到它们的肿瘤相关抗原（TAA）的肿瘤细胞。
