Intracellular processing of antigens is crucial for the generation of T cell immunity towards cancers, since cleaved protein products are the molecular targets of these adaptive lymphocytes. The majority of antigenic peptides requires the TAP transporter to gain access to the peptide loading complex in the ER lumen where they bind MHC class I (MHC-I). This pivotal role of TAP in antigen processing makes the system vulnerable for modifications in cancer cells and indeed human cancers frequently silence this gene epigenetically. Interestingly, TAP-independent processing pathways then become apparent and partly restore MHC class I presentation with alternative peptides. In this review we discuss recent insights on how TAP-independent processing of immunogenic peptides occurs, and how these antigens can be exploited for cancer immunotherapy.

中文翻译：

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TAP 或不 TAP：癌症免疫治疗的替代肽。

抗原的细胞内加工对于产生针对癌症的 T 细胞免疫至关重要，因为裂解的蛋白质产物是这些适应性淋巴细胞的分子靶标。大多数抗原肽需要 TAP 转运蛋白才能进入 ER 腔中的肽负载复合物，在该复合物中它们与 MHC I 类 (MHC-I) 结合。TAP 在抗原加工中的关键作用使得该系统容易受到癌细胞修饰的影响，实际上人类癌症经常在表观遗传上沉默该基因。有趣的是，不依赖于 TAP 的加工途径随后变得明显，并用替代肽部分恢复了 MHC I 类呈递。在这篇综述中，我们讨论了关于免疫原性肽的 TAP 非依赖性加工是如何发生的，以及这些抗原如何用于癌症免疫治疗的最新见解。