Department of Morphological Sciences, Cell and Molecular Biology and Histology, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania.
Department of Radiology and Medical Imaging, Fundeni Clinical Institute, 022328 Bucharest, Romania.
Int J Mol Sci. 2024 Sep 6;25(17):9659. doi: 10.3390/ijms25179659.
Predictive biomarkers for immune checkpoint inhibitors (ICIs) in solid tumors such as melanoma, hepatocellular carcinoma (HCC), colorectal cancer (CRC), non-small cell lung cancer (NSCLC), endometrial carcinoma, renal cell carcinoma (RCC), or urothelial carcinoma (UC) include programmed cell death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), defective deoxyribonucleic acid (DNA) mismatch repair (dMMR), microsatellite instability (MSI), and the tumor microenvironment (TME). Over the past decade, several types of ICIs, including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, anti-programmed cell death 1 (PD-1) antibodies, anti-programmed cell death ligand 1 (PD-L1) antibodies, and anti-lymphocyte activation gene-3 (LAG-3) antibodies have been studied and approved by the Food and Drug Administration (FDA), with ongoing research on others. Recent studies highlight the critical role of the gut microbiome in influencing a positive therapeutic response to ICIs, emphasizing the importance of modeling factors that can maintain a healthy microbiome. However, resistance mechanisms can emerge, such as increased expression of alternative immune checkpoints, T-cell immunoglobulin (Ig), mucin domain-containing protein 3 (TIM-3), LAG-3, impaired antigen presentation, and alterations in the TME. This review aims to synthesize the data regarding the interactions between microbiota and immunotherapy (IT). Understanding these mechanisms is essential for optimizing ICI therapy and developing effective combination strategies.
在黑色素瘤、肝细胞癌 (HCC)、结直肠癌 (CRC)、非小细胞肺癌 (NSCLC)、子宫内膜癌、肾细胞癌 (RCC) 或尿路上皮癌 (UC) 等实体瘤中，免疫检查点抑制剂 (ICIs) 的预测生物标志物包括程序性细胞死亡配体 1 (PD-L1) 表达、肿瘤突变负担 (TMB)、缺陷的脱氧核糖核酸 (DNA) 错配修复 (dMMR)、微卫星不稳定性 (MSI) 和肿瘤微环境 (TME)。在过去的十年中，包括细胞毒性 T 淋巴细胞相关蛋白 4 (CTLA-4) 抑制剂、抗程序性细胞死亡 1 (PD-1) 抗体、抗程序性细胞死亡配体 1 (PD-L1) 抗体和抗淋巴细胞激活基因-3 (LAG-3) 抗体在内的几种类型的 ICI 已被食品和药物管理局 (FDA) 研究和批准，其他 ICI 也在进行研究。最近的研究强调了肠道微生物组在影响对 ICI 的积极治疗反应中的关键作用，强调了建模可维持健康微生物组的因素的重要性。然而，可能会出现耐药机制，例如替代免疫检查点、T 细胞免疫球蛋白 (Ig)、粘蛋白结构域蛋白 3 (TIM-3)、LAG-3 的表达增加、抗原呈递受损以及 TME 的改变。本综述旨在综合有关微生物组与免疫疗法 (IT) 之间相互作用的数据。了解这些机制对于优化 ICI 治疗和开发有效的联合策略至关重要。
