Medical Oncology Department, Portuguese Oncolology Institute of Coimbra Francisco Gentil, Avenida Bissaya Barreto, 98, 3000-075, Coimbra, Portugal.
Immunology Institute, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Med Oncol. 2021 Mar 31;38(5):51. doi: 10.1007/s12032-021-01497-8.
The interplay between cancer and the immune system has been under investigation for more than a century. Immune checkpoint inhibitors have changed the outcome of several tumors; however, there is a significant percentage of patients presenting resistance to immunotherapy. Besides the action mechanism, it is essential to unravel this complex interplay between host immune system and tumorigenesis to determine an immune profile as a predictive factor to immune checkpoint blockade agents. Tumor expression of programmed death-ligand 1 (PD-L1), tumor mutational burden, or mismatch repair deficiency are recognized predictive biomarkers to immunotherapy but are insufficient to explain the response rates and heterogeneity across tumor sites. Therefore, it is crucial to explore the role of the tumor microenvironment in the diversity and clonality of tumor-infiltrating immune cells since different checkpoint molecules play an influential role in cytotoxic T cell activation. Moreover, cytokines, chemokines, and growth factors regulated by epigenetic factors play a complex part. Peripheral immune cells expressing PD-1/PD-L1 and the biologic roles of soluble immune checkpoint molecules are the subject of new lines of investigation. This article addresses some of the new molecules and mechanisms studied as possible predictive biomarkers to immunotherapy, linked with the concept of immune dynamics monitoring.
癌症与免疫系统的相互作用已经研究了一个多世纪。免疫检查点抑制剂改变了几种肿瘤的结局；然而，仍有相当比例的患者对免疫疗法产生耐药性。除了作用机制外，揭示宿主免疫系统与肿瘤发生之间的这种复杂相互作用至关重要，以确定免疫特征作为免疫检查点阻断剂的预测因素。肿瘤程序性死亡配体 1（PD-L1）的表达、肿瘤突变负担或错配修复缺陷被认为是免疫治疗的预测性生物标志物，但不足以解释肿瘤部位的反应率和异质性。因此，探索肿瘤微环境在肿瘤浸润免疫细胞的多样性和克隆性中的作用至关重要，因为不同的检查点分子在细胞毒性 T 细胞激活中发挥着重要作用。此外，受表观遗传因素调控的细胞因子、趋化因子和生长因子也起着复杂的作用。表达 PD-1/PD-L1 的外周免疫细胞和可溶性免疫检查点分子的生物学作用是新的研究方向。本文讨论了一些作为免疫治疗预测性生物标志物的新分子和机制，这些标志物与免疫动力学监测的概念有关。
