Identification and Characterization of Neoantigens As Well As Respective Immune Responses in Cancer Patients.
Identification and Characterization of Neoantigens As Well As Respective Immune Responses in Cancer Patients.
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DOI：
10.3389/fimmu.2017.01702
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发表时间：
2017
影响因子：
7.3
通讯作者：
Krackhardt AM
中科院分区：
文献类型：
--
作者：
Bräunlein E;Krackhardt AM
癌症免疫治疗最近已成为治疗各种晚期恶性肿瘤的有力工具。特别地，免疫检查点调节剂如抗CTLA 4或抗PD-1/PD-L1抗体的治疗应用已经在广泛的恶性疾病中显示出功效。虽然这些免疫调节剂的药效学是复杂的，但最近的研究强烈支持这样的观点，即在代表新抗原的肿瘤细胞上呈递的改变的肽配体可能在由抗CTLA 4和抗PD-1抗体激活的T细胞的肿瘤排斥中起重要作用。新抗原可以具有不同的来源，如病毒和突变蛋白。此外，翻译后修饰和改变的抗原加工也可能有助于新抗原肽配体景观。目前，不同的靶点鉴定方法与针对这种新抗原的自体和非自体T细胞应答的后续表征相结合。需要额外的努力来阐明新抗原，免疫优势，各自的T细胞反应和肿瘤微环境的关键特征和相互依赖性，以确定有效的T细胞介导的肿瘤排斥反应中涉及的决定性决定因素。这篇评论的重点是我们目前的知识，识别和表征这样的新抗原以及各自的T细胞反应。最后，它与未来进一步改善恶性疾病免疫策略相关的挑战有关。
Cancer immunotherapy has recently emerged as a powerful tool for the treatment of diverse advanced malignancies. In particular, therapeutic application of immune checkpoint modulators, such as anti-CTLA4 or anti-PD-1/PD-L1 antibodies, have shown efficacy in a broad range of malignant diseases. Although pharmacodynamics of these immune modulators are complex, recent studies strongly support the notion that altered peptide ligands presented on tumor cells representing neoantigens may play an essential role in tumor rejection by T cells activated by anti-CTLA4 and anti-PD-1 antibodies. Neoantigens may have diverse sources as viral and mutated proteins. Moreover, posttranslational modifications and altered antigen processing may also contribute to the neoantigenic peptide ligand landscape. Different approaches of target identification are currently applied in combination with subsequent characterization of autologous and non-self T-cell responses against such neoantigens. Additional efforts are required to elucidate key characteristics and interdependences of neoantigens, immunodominance, respective T-cell responses, and the tumor microenvironment in order to define decisive determinants involved in effective T-cell-mediated tumor rejection. This review focuses on our current knowledge of identification and characterization of such neoantigens as well as respective T-cell responses. It closes with challenges to be addressed in future relevant for further improvement of immunotherapeutic strategies in malignant diseases.