免疫编辑
免疫疗法
表位
免疫系统
癌症
免疫原性
免疫学
计算生物学
T细胞
细胞毒性T细胞
免疫
癌症免疫疗法
癌症疫苗
癌症研究
生物
抗原
遗传学
体外
作者
Ravi Gupta,Fenge Li,Jason Roszik,Gregory Lizée
出处
期刊:Cancer Discovery
[American Association for Cancer Research]
日期:2021-03-15
卷期号:11 (5): 1024-1039
被引量:51
标识
DOI:10.1158/2159-8290.cd-20-1575
摘要
Immunotherapeutic manipulation of the antitumor immune response offers an attractive strategy to target genomic instability in cancer. A subset of tumor-specific somatic mutations can be translated into immunogenic and HLA-bound epitopes called neoantigens, which can induce the activation of helper and cytotoxic T lymphocytes. However, cancer immunoediting and immunosuppressive mechanisms often allow tumors to evade immune recognition. Recent evidence also suggests that the tumor neoantigen landscape extends beyond epitopes originating from nonsynonymous single-nucleotide variants in the coding exome. Here we review emerging approaches for identifying, prioritizing, and immunologically targeting personalized neoantigens using polyvalent cancer vaccines and T-cell receptor gene therapy. SIGNIFICANCE: Several major challenges currently impede the clinical efficacy of neoantigen-directed immunotherapy, such as the relative infrequency of immunogenic neoantigens, suboptimal potency and priming of de novo tumor-specific T cells, and tumor cell-intrinsic and -extrinsic mechanisms of immune evasion. A deeper understanding of these biological barriers could help facilitate the development of effective and durable immunotherapy for any type of cancer, including immunologically "cold" tumors that are otherwise therapeutically resistant.
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