At the Cutting Edge against Cancer: A Perspective on Immunoproteasome and Immune Checkpoints Modulation as a Potential Therapeutic Intervention.
At the Cutting Edge against Cancer: A Perspective on Immunoproteasome and Immune Checkpoints Modulation as a Potential Therapeutic Intervention.
复制标题
DOI：
10.3390/cancers13194852
复制
发表时间：
2021-09-28
期刊：
影响因子：
5.2
通讯作者：
Marini S
中科院分区：
文献类型：
--
作者：
Tundo GR;Sbardella D;Oddone F;Kudriaeva AA;Lacal PM;Belogurov AA Jr;Graziani G;Marini S
免疫蛋白酶体在抗原肽的产生中起着关键作用。免疫检查点疗法是晚期/转移性肿瘤的一线治疗，为了提高其疗效，必须更广泛地了解癌细胞处理抗原库的动力学。本次审查的范围是提供一个图片的免疫蛋白酶体在抗原呈递的作用，燃料的基础上调制这种蛋白水解复合物和免疫检查点的新的治疗干预的假设。免疫蛋白酶体是一种非典型形式的蛋白酶体，具有优化的酶学性质，用于产生与I类MHC分子复合的抗原肽。这种酶的性质使其活性的调节成为一个有前途的研究领域。尽管如此，免疫疗法已成为晚期/转移性肿瘤的一线治疗方法，显著改善了预期寿命，尽管并非所有患者都能获得长期的临床获益。为了增强目前可用的免疫疗法的功效并能够开发新的策略，需要对癌细胞处理抗原库的动力学有更广泛的了解。因此，更好地了解免疫蛋白酶体在抗原加工中的作用及其调节的治疗意义是强制性的。对蛋白酶体调节剂和免疫检查点抑制剂之间潜在串扰的研究可以为各种癌症提供新的视角和未探索的治疗选择。
Immunoproteasome plays a key role in the generation of antigenic peptides. Immune checkpoints therapy is a front-line treatment of advanced/metastatic tumors, and to improve its efficacy, a broader knowledge of the dynamics of antigen repertoire processing by cancer cells is mandatory. The scope of this review is to offer a picture of the role of immunoproteasome in antigen presentation to fuel the hypothesis of novel therapeutic interventions based on the modulation of this proteolytic complex and immune checkpoints. Immunoproteasome is a noncanonical form of proteasome with enzymological properties optimized for the generation of antigenic peptides presented in complex with class I MHC molecules. This enzymatic property makes the modulation of its activity a promising area of research. Nevertheless, immunotherapy has emerged as a front-line treatment of advanced/metastatic tumors providing outstanding improvement of life expectancy, even though not all patients achieve a long-lasting clinical benefit. To enhance the efficacy of the currently available immunotherapies and enable the development of new strategies, a broader knowledge of the dynamics of antigen repertoire processing by cancer cells is needed. Therefore, a better understanding of the role of immunoproteasome in antigen processing and of the therapeutic implication of its modulation is mandatory. Studies on the potential crosstalk between proteasome modulators and immune checkpoint inhibitors could provide novel perspectives and an unexplored treatment option for a variety of cancers.
登录
查看更多内容
髓磷脂碱性蛋白的不依赖于泛素的蛋白酶体降解有助于神经退行性自身免疫的发展。
DOI：
10.1096/fj.14-259333
发表时间：
2015-05
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
Belogurov A Jr;Kuzina E;Kudriaeva A;Kononikhin A;Kovalchuk S;Surina Y;Smirnov I;Lomakin Y;Bacheva A;Stepanov A;Karpova Y;Lyupina Y;Kharybin O;Melamed D;Ponomarenko N;Sharova N;Nikolaev E;Gabibov A
通讯作者：
Gabibov A
影响因子：
5.2
作者：
Atkinson, Stuart P.;Collin, Joseph;Armstrong, Lyle
通讯作者：
Armstrong, Lyle
DOI：
10.1084/jem.179.3.901
发表时间：
1994-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Boes B;Hengel H;Ruppert T;Multhaup G;Koszinowski UH;Kloetzel PM
通讯作者：
Kloetzel PM
PD-1检查点途径的分子和生化方面。
DOI：
10.1056/nejmra1514296
发表时间：
2016-11-03
期刊：
The New England journal of medicine
影响因子：
--
作者：
Boussiotis VA
通讯作者：
Boussiotis VA
影响因子：
2.7
作者：
AKI, M;SHIMBARA, N;ICHIHARA, A
通讯作者：
ICHIHARA, A