The first hypotheses about how the immune system affects cancers were proposed in the early 20th century. These early concepts about cancer immunosurveillance were further developed in the decades that followed, but a detailed understanding of cancer immunity remained elusive. It was only recently, through the advent of high-throughput technologies, that scientists gained the ability to profile tumors with a resolution that allowed for granular assessment of both tumor cells and the tumor microenvironment. The advent of immune checkpoint inhibitors (ICIs), which have proven to be effective cancer therapies in many malignancies, has spawned great interest in developing biomarkers for efficacy, an endeavor that highlighted the value of dissecting tumor immunity using large-scale methods. Response to ICI therapy has been shown to be a highly complex process, where the dynamics of tumor and immune cells is key to success. The need to understand the biologic mechanisms at the tumor–immune interface has given rise to the field of cancer immunogenomics, a discipline that aims to bridge the gap between cancer genomics and classical immunology. We provide a broad overview of this emerging branch of translational science, summarizing common platforms used and recent discoveries in the field, which are having direct clinical implications. Our discussion will be centered around the genetic foundations governing tumor immunity and molecular determinants associated with clinical benefit from ICI therapy. We emphasize the importance of molecular diversity as a driver of anti-tumor immunity and discuss how these factors can be probed using genomic approaches.

中文翻译：

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基于基因组学的免疫肿瘤学：弥合免疫学和肿瘤生物学之间的差距

关于免疫系统如何影响癌症的第一个假设是在 20 世纪初提出的。这些关于癌症免疫监视的早期概念在随后的几十年中得到了进一步发展，但对癌症免疫的详细了解仍然难以捉摸。直到最近，通过高通量技术的出现，科学家们才获得了以可对肿瘤细胞和肿瘤微环境进行精细评估的分辨率来分析肿瘤的能力。免疫检查点抑制剂（ICIs）的出现已被证明是许多恶性肿瘤的有效癌症疗法，引发了人们对开发疗效生物标志物的极大兴趣，这一努力凸显了使用大规模方法剖析肿瘤免疫的价值。ICI 治疗的反应已被证明是一个高度复杂的过程，其中肿瘤和免疫细胞的动态是成功的关键。了解肿瘤-免疫界面的生物学机制的需要催生了癌症免疫基因组学领域，该学科旨在弥合癌症基因组学和经典免疫学之间的差距。我们对这一新兴的转化科学分支进行了广泛的概述，总结了该领域所使用的常用平台和最新发现，这些发现具有直接的临床意义。我们的讨论将围绕控制肿瘤免疫的遗传基础以及与 ICI 治疗临床获益相关的分子决定因素展开。我们强调分子多样性作为抗肿瘤免疫驱动因素的重要性，并讨论如何使用基因组方法探测这些因素。