Lack of responsiveness to checkpoint inhibitors is a central problem in the modern era of cancer immunotherapy. Tumor neoantigens are critical targets of the host antitumor immune response, and their presence correlates with the efficacy of immunotherapy treatment. Many studies involving assessment of tumor neoantigens principally focus on total neoantigen load, which simplistically treats all neoantigens equally. Neoantigen load has been linked with treatment response and prognosis in some studies but not others. We developed a Cauchy-Schwarz index of Neoantigens (CSiN) score to better account for the degree of concentration of immunogenic neoantigens in truncal mutations. Unlike total neoantigen load determinations, CSiN incorporates the effect of both clonality and MHC binding affinity of neoantigens when characterizing tumor neoantigen profiles. By analyzing the clinical responses in 501 treated patients with cancer (with most receiving checkpoint inhibitors) and the overall survival of 1978 patients with cancer at baseline, we showed that CSiN scores predict treatment response to checkpoint inhibitors and prognosis in patients with melanoma, lung cancer, and kidney cancer. CSiN score substantially outperformed prior genetics-based prediction methods of responsiveness and fills an important gap in research involving assessment of tumor neoantigen burden.

中文翻译：

---

具有CSiN评分的肿瘤新抗原性评估结合了克隆性和免疫原性，以预测免疫治疗的结果。

对检查点抑制剂缺乏响应是现代癌症免疫治疗中的一个主要问题。肿瘤新抗原是宿主抗肿瘤免疫反应的关键靶标，它们的存在与免疫疗法的疗效相关。许多涉及评估肿瘤新抗原的研究主要集中在总新抗原负荷上，其简单地将所有新抗原同等对待。在一些研究中，新抗原负荷与治疗反应和预后相关，而在其他研究中却没有。我们开发了新抗原柯西·舒瓦兹指数（CSiN）评分，以更好地说明截断突变中免疫原性新抗原的浓度。与确定总的新抗原量不同，当表征肿瘤新抗原概况时，CSiN结合了新抗原的克隆性和MHC结合亲和力的作用。通过分析501名接受治疗的癌症患者（大多数接受检查点抑制剂）的临床反应以及1978年基线时的癌症患者的整体存活率，我们显示CSiN评分可预测黑素瘤，肺癌患者对检查点抑制剂的治疗反应和预后和肾癌。CSiN评分大大优于先前基于遗传学的反应性预测方法，并填补了涉及评估肿瘤新抗原负担的研究中的重要空白。我们发现CSiN分数可预测黑色素瘤，肺癌和肾癌患者对检查点抑制剂的治疗反应和预后。CSiN评分大大优于先前基于遗传学的反应性预测方法，并填补了涉及评估肿瘤新抗原负担的研究中的重要空白。我们发现CSiN分数可预测黑色素瘤，肺癌和肾癌患者对检查点抑制剂的治疗反应和预后。CSiN评分大大优于先前基于遗传学的反应性预测方法，并填补了涉及评估肿瘤新抗原负担的研究中的重要空白。