Gustave Roussy Comprehensive Cancer Institute, Villejuif, France.
Université Paris Saclay, Faculty of Medicine, Le Kremlin-Bicêtre, France.
Nat Rev Clin Oncol. 2021 Sep;18(9):591-602. doi: 10.1038/s41571-021-00508-x. Epub 2021 May 11.
Many tumour antigens that do not arise from cancer cell-specific mutations are targets of humoral and cellular immunity despite their expression on non-malignant cells. Thus, in addition to the expected ability to detect mutations and stress-associated shifts in the immunoproteome and immunopeptidome (the sum of MHC class I-bound peptides) unique to malignant cells, the immune system also recognizes antigens expressed in non-malignant cells, which can result in autoimmune reactions against non-malignant cells from the tissue of origin. These autoimmune manifestations include, among others, vitiligo, thyroiditis and paraneoplastic syndromes, concurrent with melanoma, thyroid cancer and non-small-cell lung cancer, respectively. Importantly, despite the undesirable effects of these symptoms, such events can have prognostic value and correlate with favourable disease outcomes, suggesting 'beneficial autoimmunity'. Similarly, the occurrence of dermal and endocrine autoimmune adverse events in patients receiving immune-checkpoint inhibitors can have a positive predictive value for therapeutic outcomes. Neoplasias derived from stem cells deemed 'not essential' for survival (such as melanocytes, thyroid cells and most cells in sex-specific organs) have a particularly good prognosis, perhaps because the host can tolerate autoimmune reactions that destroy tumour cells at some cost to non-malignant tissues. In this Perspective, we discuss examples of spontaneous as well as therapy-induced autoimmunity that correlate with favourable disease outcomes and make a strong case in favour of this 'beneficial autoimmunity' being important not only in patients with advanced-stage disease but also in cancer immunosurveillance.
许多肿瘤抗原并非来自癌细胞特异性突变，尽管它们在非恶性细胞上表达，但仍是体液和细胞免疫的靶标。因此，除了预期能够检测到恶性细胞特有的突变和应激相关的免疫蛋白质组和免疫肽组（与 MHC I 结合的肽的总和）变化外，免疫系统还识别在非恶性细胞中表达的抗原，这可能导致针对源自组织的非恶性细胞的自身免疫反应。这些自身免疫表现包括，除其他外，白癜风、甲状腺炎和副肿瘤综合征，分别与黑色素瘤、甲状腺癌和非小细胞肺癌同时发生。重要的是，尽管这些症状存在不良影响，但这些事件可能具有预后价值，并与有利的疾病结果相关，提示“有益的自身免疫”。同样，接受免疫检查点抑制剂治疗的患者出现皮肤和内分泌自身免疫不良事件，对治疗结果具有阳性预测价值。来自被认为对生存“非必需”的干细胞的肿瘤（如黑色素细胞、甲状腺细胞和大多数性别特异性器官中的细胞）具有特别好的预后，这也许是因为宿主可以耐受破坏肿瘤细胞的自身免疫反应，而以牺牲非恶性组织为代价。在本观点中，我们讨论了与有利的疾病结果相关的自发和治疗诱导的自身免疫的例子，并强烈支持这种“有益的自身免疫”不仅对晚期疾病患者而且对癌症免疫监视都很重要。
