The remarkable success of immune checkpoint inhibitors demonstrates the potential of tumour-specific CD8⁺ T cells to prevent and treat cancer. Although the number of lives saved by immunotherapy mounts, only a relatively small fraction of patients are cured. Here, we review two of the factors that limit the application of CD8⁺ T cell immunotherapies: difficulties in identifying tumour-specific peptides presented by MHC class I molecules and the ability of tumour cells to impair antigen presentation as they evolve under T cell selection. We describe recent advances in understanding how peptides are generated from non-canonical translation of defective ribosomal products, relate this to the dysregulated translation that is a feature of carcinogenesis and propose dysregulated translation as an important new source of tumour-specific peptides. We discuss how the synthesis and function of components of the antigen-processing and presentation pathway, including the recently described immunoribosome, are manipulated by tumours for immunoevasion and point to common druggable targets that may enhance immunotherapy.

免疫检查点抑制剂的显着成功证明了肿瘤特异性 CD8 ⁺ T 细胞预防和治疗癌症的潜力。尽管免疫疗法挽救的生命数量不断增加，但只有相对一小部分患者被治愈。^{在这里，我们回顾一下限制CD8 +}应用的两个因素T 细胞免疫疗法：难以识别由 MHC I 类分子呈递的肿瘤特异性肽，以及肿瘤细胞在 T 细胞选择下进化时削弱抗原呈递的能力。我们描述了了解肽如何从有缺陷的核糖体产物的非规范翻译中产生的最新进展，将其与作为致癌作用特征的失调翻译联系起来，并提出失调翻译作为肿瘤特异性肽的重要新来源。我们讨论了抗原加工和呈递途径成分的合成和功能，包括最近描述的免疫核糖体，如何被肿瘤操纵以进行免疫逃逸，并指出可能增强免疫治疗的常见药物靶点。