Antigen presentation via the major histocompatibility complex (MHC) is essential for anti-tumor immunity. However, the rules that determine which tumor-derived peptides will be immunogenic are still incompletely understood. Here, we investigated whether constraints on peptide accessibility to the MHC due to protein subcellular location are associated with peptide immunogenicity potential. Analyzing over 380,000 peptides from studies of MHC presentation and peptide immunogenicity, we find clear spatial biases in both eluted and immunogenic peptides. We find that including parent protein location improves the prediction of peptide immunogenicity in multiple datasets. In human immunotherapy cohorts, the location was associated with a neoantigen vaccination response, and immune checkpoint blockade responders generally had a higher burden of neopeptides from accessible locations. We conclude that protein subcellular location adds important information for optimizing cancer immunotherapies.

中文翻译：

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源蛋白的亚细胞定位提高了免疫治疗新抗原的预测

通过主要组织相容性复合物 (MHC) 呈递抗原对于抗肿瘤免疫至关重要。然而，决定哪些肿瘤衍生肽具有免疫原性的规则仍不完全清楚。在这里，我们研究了由于蛋白质亚细胞位置而对肽进入 MHC 的限制是否与肽免疫原性潜力相关。通过分析 MHC 呈递和肽免疫原性研究中的 380,000 多个肽，我们发现洗脱肽和免疫原性肽均存在明显的空间偏差。我们发现，包括亲本蛋白位置可以提高多个数据集中肽免疫原性的预测。在人类免疫治疗队列中，该位置与新抗原疫苗接种反应相关，并且免疫检查点封锁反应者通常从可到达的位置具有更高的新肽负担。我们的结论是，蛋白质亚细胞定位为优化癌症免疫疗法增加了重要信息。