Institut de Recherche en Cancérologie de Montpellier (IRCM), Inserm U1194, Univ Montpellier, Institut du Cancer de Montpellier (ICM), Montpellier, France.
Front Immunol. 2023 Apr 26;14:1170321. doi: 10.3389/fimmu.2023.1170321. eCollection 2023.
Immune checkpoint blockade represents the latest revolution in cancer treatment by substantially increasing patients' lifetime and quality of life in multiple neoplastic pathologies. However, this new avenue of cancer management appeared extremely beneficial in a minority of cancer types and the sub-population of patients that would benefit from such therapies remain difficult to predict. In this review of the literature, we have summarized important knowledge linking cancer cell characteristics with the response to immunotherapy. Mostly focused on lung cancer, our objective was to illustrate how cancer cell diversity inside a well-defined pathology might explain sensitivity and refractoriness to immunotherapies. We first discuss how genomic instability, epigenetics and innate immune signaling could explain differences in the response to immune checkpoint blockers. Then, in a second part we detailed important notions suggesting that altered cancer cell metabolism, specific oncogenic signaling, tumor suppressor loss as well as tight control of the cGAS/STING pathway in the cancer cells can be associated with resistance to immune checkpoint blockade. At the end, we discussed recent evidences that could suggest that immune checkpoint blockade as first line therapy might shape the cancer cell clones diversity and give rise to the appearance of novel resistance mechanisms.
免疫检查点阻断代表了癌症治疗的最新革命，在多种肿瘤病理学中大大提高了患者的寿命和生活质量。然而，这种癌症管理的新途径在少数癌症类型和受益于此类治疗的患者亚群中表现出极大的益处，仍然难以预测。在对文献的综述中，我们总结了将癌细胞特征与免疫治疗反应联系起来的重要知识。我们主要关注肺癌，旨在说明在明确的病理学中，癌细胞多样性如何解释对免疫疗法的敏感性和耐药性。我们首先讨论了基因组不稳定性、表观遗传学和先天免疫信号如何解释对免疫检查点抑制剂反应的差异。然后，在第二部分，我们详细介绍了一些重要的概念，表明癌细胞代谢的改变、特定的致癌信号、肿瘤抑制因子的丧失以及癌细胞中 cGAS/STING 途径的严格控制可能与免疫检查点阻断的耐药性相关。最后，我们讨论了最近的证据，这些证据可能表明，作为一线治疗的免疫检查点阻断可能会影响癌症细胞克隆的多样性，并导致新的耐药机制的出现。
