首页> 中文期刊>中华放射肿瘤学杂志 >大剂量分割放疗与肿瘤免疫——新概念与新结合

大剂量分割放疗与肿瘤免疫——新概念与新结合

摘要

Modern immunology has established that tumor immune escape is associated with hidden or missing tumor-specific antigens and tumor-associated antigens,as well as immune suppressors that are released from tumor cells to inhibit the immune cytotoxicity and antigen-presenting cells (APCs).The changes in tumor microenvironment have an impact on tumor immunity and treatment outcomes.The immune effects finally depend on activation and inhibition of T cell receptors and other co-regulated receptors (CD28,CD80/CD86,and CTLA-4) in spite of the existence of APCs and cytotoxic T lymphocytes in tumor microenvironment.Recent studies have revealed that radiotherapy induced not only DNA damage but also immunogenesis in tumor cells.Both conventionally fractionated radiotherapy and hypofractionated radiotherapy can induce immunogenesis in tumor cells.Immunogenic regulation makes many tumor antigens expressed in cells exposed to irradiation,which induces immune recognition and cytotoxicity;cell content (DNA,HMGB1,etc.) released from dead immunogenic cells can trigger immune effects and in situ tumor vaccination,which further induce an abscopal effect of radiotherapy.A lot of anti-tumor immunotherapy fails to achieve satisfactory treatment outcomes.Therefore,how to combine radiotherapy,especially stereotactic body radiotherapy,with anti-tumor immunotherapy has recently become a new challenge for researchers.%现代免疫学认为肿瘤的逃逸机制与肿瘤特异抗原(TSA)和肿瘤相关抗原(TAA)的隐藏、丢失,肿瘤自身分泌一些免疫抑制因子抑制免疫杀伤和抗原呈递细胞(APC)有关.肿瘤微环境的变化对肿瘤免疫变化及肿瘤治疗的转归也有影响.在肿瘤局部,尽管抗原呈递细胞(APC)和免疫效应细胞CTL都存在,但是,免疫作用效果却取决于T细胞受体(TCR)和其他共调节受体(CD28、CD80/CD86、CTLA-4)的活化或抑制.近年来研究发现,放疗不仅能造成肿瘤细胞DNA损伤,还能引起肿瘤细胞的免疫原性.无论常规分割照射还是大剂量分割照射都可以产生肿瘤的至免疫原性(Immunogenesis).至免疫性细胞调节能使受照射细胞表达多种抗原,使细胞易于免疫识别和杀伤;至免疫原性细胞死亡所释放的细胞内容物(如DNA、HMGB1等)能够刺激免疫反应,产生“原位疫苗”作用,进而产生放疗的远隔效应.许多抗肿瘤免疫治疗方法没能达到令人满意的效果,如何利用放疗,特别是SBRT方法与抗肿瘤免疫治疗结合成为近年来的研究新课题.

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