Resistance to immune checkpoint inhibitors (ICIs) represents a major challenge for the effective treatment of non-small cell lung cancer (NSCLC). Tumor heterogeneity has been identified as an important mechanism of treatment resistance in cancer and has been increasingly implicated in ICI resistance. The diversity and clonality of tumor neoantigens, which represent the target epitopes for tumor-specific immune cells, have been shown to impact the efficacy of immunotherapy. Advances in genomic techniques have further enhanced our understanding of clonal landscapes within NSCLC and their evolution in response to therapy. In this review, we examine the role of tumor heterogeneity during immune surveillance in NSCLC and highlight its spatial and temporal evolution as revealed by modern technologies. We explore additional sources of heterogeneity, including epigenetic and metabolic factors, that have come under greater scrutiny as potential mediators of the immune response. We finally discuss the implications of tumor heterogeneity on the efficacy of ICIs and highlight potential strategies for overcoming therapeutic resistance.
免疫检查点抑制剂（ICIs）耐药是非小细胞肺癌（NSCLC）有效治疗面临的主要挑战。肿瘤异质性已被确定为癌症治疗耐药的重要机制，并日益被认为与ICI耐药相关。作为肿瘤特异性免疫细胞的靶向表位，肿瘤新抗原的多样性与克隆性已被证实会影响免疫治疗效果。基因组学技术的进步进一步加深了我们对NSCLC内部克隆景观及其在治疗过程中演变的理解。本综述探讨了肿瘤异质性在NSCLC免疫监视中的作用，重点阐述了现代技术所揭示的异质性在空间与时间维度上的动态演变。我们进一步探究了包括表观遗传和代谢因素在内的其他异质性来源，这些因素作为免疫反应的潜在调节介质正受到日益密切的关注。最后，我们讨论了肿瘤异质性对ICIs疗效的影响，并着重提出了克服治疗耐药性的潜在策略。
肿瘤(癌症)患者之家