Identification of Neoantigens in Cancer Cells as Targets for Immunotherapy.
Identification of Neoantigens in Cancer Cells as Targets for Immunotherapy.
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DOI：
10.3390/ijms23052594
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发表时间：
2022-02-26
影响因子：
5.6
通讯作者：
Fujii SI
中科院分区：
文献类型：
--
作者：
Okada M;Shimizu K;Fujii SI
免疫检查点阻断（ICB）疗法的临床益处已被广泛报道。在癌症患者中，研究人员已经证明了抗肿瘤细胞毒性T细胞的临床潜力，可以通过ICB重新激活或增强。与自身抗原相比，肿瘤体细胞突变产生的新抗原被认为是肿瘤中理想的免疫靶点。候选肿瘤新抗原可以通过免疫基因组学或免疫肽组学方法鉴定。新抗原的鉴定已经揭示了几点临床相关性。例如，肿瘤突变负荷（TMB）可能是免疫治疗的指标。在各种癌症中，伴随新抗原负荷的突变率可以指示免疫疗法。此外，在ICB治疗中，T细胞可以根除错配修复缺陷型肿瘤。因此，使用疫苗或过继性T细胞转移靶向新抗原的免疫疗法是潜在的创新策略。然而，需要大量的努力来鉴定最佳表位。本文综述了近年来新生抗原的研究进展，并对基于新生抗原的临床前和临床研究进行了讨论。我们还讨论了这些新的治疗策略的临床应用之前，仍然需要解决的问题可以实现。
The clinical benefits of immune checkpoint blockage (ICB) therapy have been widely reported. In patients with cancer, researchers have demonstrated the clinical potential of antitumor cytotoxic T cells that can be reinvigorated or enhanced by ICB. Compared to self-antigens, neoantigens derived from tumor somatic mutations are believed to be ideal immune targets in tumors. Candidate tumor neoantigens can be identified through immunogenomic or immunopeptidomic approaches. Identification of neoantigens has revealed several points of the clinical relevance. For instance, tumor mutation burden (TMB) may be an indicator of immunotherapy. In various cancers, mutation rates accompanying neoantigen loads may be indicative of immunotherapy. Furthermore, mismatch repair-deficient tumors can be eradicated by T cells in ICB treatment. Hence, immunotherapies using vaccines or adoptive T-cell transfer targeting neoantigens are potential innovative strategies. However, significant efforts are required to identify the optimal epitopes. In this review, we summarize the recent progress in the identification of neoantigens and discussed preclinical and clinical studies based on neoantigens. We also discuss the issues remaining to be addressed before clinical applications of these new therapeutic strategies can be materialized.
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影响因子：
64.5
作者：
Burger ML;Cruz AM;Crossland GE;Gaglia G;Ritch CC;Blatt SE;Bhutkar A;Canner D;Kienka T;Tavana SZ;Barandiaran AL;Garmilla A;Schenkel JM;Hillman M;de Los Rios Kobara I;Li A;Jaeger AM;Hwang WL;Westcott PMK;Manos MP;Holovatska MM;Hodi FS;Regev A;Santagata S;Jacks T
通讯作者：
Jacks T
影响因子：
32.4
作者：
Abelin JG;Keskin DB;Sarkizova S;Hartigan CR;Zhang W;Sidney J;Stevens J;Lane W;Zhang GL;Eisenhaure TM;Clauser KR;Hacohen N;Rooney MS;Carr SA;Wu CJ
通讯作者：
Wu CJ
影响因子：
24.8
作者：
Ahmadzadeh, Mojgan;Pasetto, Anna;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.
影响因子：
15.9
作者：
Biernacki, Melinda A.;Foster, Kimberly A.;Bleakley, Marie
通讯作者：
Bleakley, Marie
影响因子：
15.9
作者：
Cohen, Cyrille J.;Gartner, Jared J.;Robbins, Paul F.
通讯作者：
Robbins, Paul F.