Nowadays,tumor immunotherapies have achieved unprecedented therapeutic effects in the treatment of cancer[1].Accumulating evidences indicate that tumor immunotherapies intrinsically depend on the specific triggering of T cells by neoantigens,and the quantity and quality of neoantigens are likely to be the core factors affecting the immunotherapeutic effect of cancers[2].Neoantigens are essentially MHC-I presented short peptides,which are mainly arised from proteasome-degraded mutant proteins.Although a large number of somatic mutations existed in tumor cells,neoantigens are still scarce.Notably,the generation of neoantigens can be regulated.Lu et al.[3]found that enriching neoantigens of cancers by regulating the mRNA splicing process can trigger anti-tumor T cell response or enhance checkpoint immunotherapy to inhibit tumor growth.This discovery indicated that effective positive regulation of tumor immunotherapies can be achieved by increasing the abundance of neoantigens.However,this strategy lacks tumor specificity.Additionally,Fidanza et ai.[4]regulated the degradation process of the vaccine in proteasome by designing a single tyrosine substitution(Y6 PepⅧ)to strengthen the cellular anti-tumor immune response and increase the survival rate of mice,which implies that regulating the degradation of mutant proteins may be another effective way to enrich tumor neoantigens.

Xuan-kun Chen;Wen-bin Zhao;Zhan Zhou;Ji Cao

Institute of Pharmacology and Toxicology,Zhejiang Province Key Laboratory of Anti-Cancer Drug Research,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China;The Innovation Institute for Artificial Intelligence in Medicine,Zhejiang University,Hangzhou 310058,China;Institute of Drug Metabolism and Pharmaceutical Analysis,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China;Cancer Center of Zhejiang University,Hangzhou 310058,China

中国药理学报（英文版）

[1]Xuan-kun Chen;Wen-bin Zhao;Zhan Zhou;Ji Cao-.Tumor immunity:a novel dimension for PROTACs to conquer cancer?)[J].中国药理学报（英文版）,2022(08):2171-2172

Neoantigens,Fidanza,Pep

Tumor,immunity,novel,dimension,PROTACs,conquer,Nowadays,tumor,immunotherapies,have,achieved,unprecedented,effects,treatment,Accumulating,evidences,that,intrinsically,depend,triggering,cells,by,neoantigens,quantity,quality,are,likely,core,factors,affecting,immunotherapeutic,cancers,essentially,MHC,presented,short,peptides,which,mainly,arised,from,proteasome,degraded,mutant,proteins,Although,large,number,somatic,mutations,existed,still,scarce,Notably,generation,regulated,Lu,et,found,enriching,regulating,splicing,process,response,enhance,checkpoint,immunotherapy,inhibit,growth,This,discovery,indicated,effective,positive,regulation,increasing,abundance,However,this,strategy,lacks,specificity,Additionally,degradation,vaccine,designing,single,tyrosine,substitution,Y6,strengthen,cellular,immune,increase,survival,mice,implies,may,another,way

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