新抗原靶向治疗为癌症免疫治疗带来了一系列好处，但具有肿瘤排斥能力的肽靶点的鉴定仍然是一个限制。为了更好地定义决定肿瘤排斥潜力的标准，我们检查了针对几个不同新抗原靶标诱导的高强度 T 细胞反应以消退 MC38 肿瘤的能力。令人惊讶的是，尽管疫苗诱导的 T 细胞反应具有免疫原性，但无法使已形成的 MC38 肿瘤消退或在预防性环境中阻止肿瘤植入。然而，T 细胞对负载新抗原肽的细胞具有强大的杀伤能力。此外，肿瘤细胞的杀伤效果与细胞表面负载靶肽的 MHC 的表达水平或饱和度成正比。总的来说，这项研究证明了靶蛋白表达水平在调节新抗原的肿瘤排斥能力中发挥着关键作用。因此，除了免疫原性分析之外，纳入这一指标可能有利于抗原预测技术，以确保癌症疫苗的全面抗肿瘤效果。

Neoantigen-targeted therapy holds an array of benefits for cancer immunotherapy, but the identification of peptide targets with tumor rejection capacity remains a limitation. To better define the criteria dictating tumor rejection potential, we examined the capacity of high-magnitude T cell responses induced towards several distinct neoantigen targets to regress MC38 tumors. Surprisingly, despite their demonstrated immunogenicity, vaccine-induced T-cell responses were unable to regress established MC38 tumors or prevent tumor engraftment in a prophylactic setting. However, T cells were functional with robust killing capacity towards neoantigen peptide-loaded cells. Furthermore, tumor cell killing was rescued in proportion to the expression level or saturation of target peptide-loaded MHCs on the cell surface. Overall, this study demonstrates a pivotal role for target protein expression levels in modulating the tumor rejection capacity of neoantigens. Thus, inclusion of this metric, in addition to immunogenicity analysis, may benefit antigen prediction techniques to ensure the full anti-tumor effect of cancer vaccines.