Department of Biology, University of Rome 'Tor Vergata', Rome, Italy; IRCSS - Regina Elena National Cancer Institute, Rome, Italy; These authors contributed equally to this article; Co-senior authors.
IRCSS - Regina Elena National Cancer Institute, Rome, Italy; Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, Rome, Italy; These authors contributed equally to this article.
Trends Cell Biol. 2019 May;29(5):396-416. doi: 10.1016/j.tcb.2019.01.003. Epub 2019 Feb 11.
Evolving neoplasms accumulate non-synonymous mutations at a high rate, potentially enabling the expression of antigenic epitopes that can be recognized by the immune system. Since they are not covered by central tolerance, such tumor neoantigens (TNAs) should be under robust immune control as they surge. However, genetic defects that impair cancer cell eradication by the immune system coupled with the establishment of local immunosuppression can enable TNA accumulation, which is generally associated with improved clinical sensitivity to various immunotherapies. Here, we explore how tumor-intrinsic factors and immunological processes shape the mutational and antigenic landscape of evolving neoplasms to influence clinical responses to immunotherapy, and propose strategies to achieve robust immunological control of the disease despite disabled immunosurveillance.
不断进化的肿瘤以高速度积累非同义突变，从而潜在地能够表达可被免疫系统识别的抗原表位。由于它们不受中枢耐受的保护，因此随着它们的涌现，这些肿瘤新抗原（TNAs）应该受到强大的免疫控制。然而，某些遗传缺陷会削弱免疫系统对癌细胞的清除能力，同时导致局部免疫抑制的建立，从而使 TNA 得以积累，这通常与对各种免疫疗法的临床敏感性提高有关。在这里，我们探讨了内在肿瘤因素和免疫过程如何塑造不断进化的肿瘤的突变和抗原景观，以影响对免疫疗法的临床反应，并提出了一些策略，以实现尽管免疫监视功能受损但仍能对疾病进行强大的免疫控制。
