用于肿瘤治疗的免疫检查点抑制剂相关预测生物标志物的研究进展

Advances in predictive biomarkers associated with immune checkpoint inhibitors for tumor therapy

摘要:

恶性肿瘤是严重威胁人类健康和社会发展的疾病。传统的肿瘤治疗方法如手术、放疗、化疗和靶向治疗等不能完全满足临床治疗的需求，新兴的免疫治疗成为了肿瘤治疗领域的研究热点。免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)作为一种肿瘤免疫治疗方法，已获批用于治疗多种肿瘤，如肺癌、肝癌、胃癌和结直肠癌等。然而，ICIs在临床使用过程中，只有少数患者会出现持久反应，一些患者还会出现耐药和不良反应。因此，预测生物标志物的鉴定和开发对提高ICIs的治疗效果至关重要。肿瘤ICIs预测生物标志物主要包括肿瘤生物标志物、肿瘤微环境生物标志物、循环相关生物标志物、宿主环境生物标志物以及组合生物标志物等，对患者筛查、个体化治疗和预后评估具有重要意义。本文就肿瘤ICIs治疗预测生物标志物的前沿进展作一综述。

关键词:肿瘤;免疫治疗;免疫检查点抑制剂;预测标志物;预后;耐药

Abstract:

Malignant tumors are diseases that seriously threaten human health and social development. Traditional tumor therapies such as surgery, radiotherapy, chemotherapy and targeted therapy cannot fully meet the needs of clinical treatment, and emerging immunotherapy has become a research hotspot in the field of tumor treatment. Immune checkpoint inhibitors (ICIs) have been approved as a tumor immunotherapy method for the treatment of various tumors, such as lung cancer, liver cancer, stomach cancer and colorectal cancer, etc. However, during the clinical use of ICIs, only a small number of patients experienced durable responses, which also led to drug resistance and adverse reactions. Therefore, the identification and development of predictive biomarkers is crucial to improve the therapeutic efficacy of ICIs. The predictive biomarkers of tumor ICIs mainly include tumor biomarkers, tumor microenvironment biomarkers, circulation-related biomarkers, host environmental biomarkers and combinatorial biomarkers. They are of great significance for screening, individualized treatment and prognosis evaluation of tumor patients. This article reviews the advances of predictive markers for tumor ICIs therapy.

Key words:tumor;immunotherapy;immune checkpoint inhibitors;predictive biomarkers;prognosis;drug resistance