热疗联合免疫检查点抑制剂的基础研究和临床应用进展北大核心CSCD

恶性肿瘤传统治疗方法对晚期转移患者疗效欠佳。近年来免疫检查点抑制剂治疗发展迅速,极具潜力,但整体临床有效率不高。肿瘤通过多种机制改变肿瘤微环境,产生免疫耐药,从而大大降低了免疫检查点抑制剂的疗效。热疗不仅可发挥热效应的抗肿瘤优势,还可通过多种途径起到直接和间接免疫增敏作用,将"冷肿瘤"转变为"热肿瘤",从而多方面起到增强免疫检查点抑制剂疗效的作用。大量基础实验证明,在小鼠体内进行热疗联合免疫检查点抑制剂已取得较好效果。目前,部分正在开展的热疗联合免疫检查点抑制剂临床试验也已取得较好进展。本文从免疫检查点抑制剂、热疗、热疗联合免疫检查点抑制剂3个层面分析了联用优势,并展望了未来热疗联合免疫检查点抑制剂治疗的重点研究方向。

Progress on basic research and clinical application of hyperthermia combined with immune checkpoint inhibitors

Malignant tumor is a persistent disease that perplexes public health. Traditional treatment appears ineffective for patients with advanced metastasis. In recent years, immune checkpoint inhibitor therapy has developed rapidly and has great potential, but the overall clinical efficiency is still low. Carcinoma changes the tumor microenvironment through various mechanisms, resulting in immune resistance, which greatly reduces the efficacy of immune checkpoint inhibitors. Hyperthermia can not only play the anti-tumor advantage of thermal effect, but also play a direct and indirect immune sensitization effect through a variety of ways, transforming"cold tumor" into"hot tumor", to enhance the impact of immune checkpoint inhibitors in many patterns. Numerous basic experiments have proved that hyperthermia combined with immune checkpoint inhibitors has achieved a classy impression in mice. Presently, some ongoing clinical trials of hyperthermia combined with immune checkpoint inhibitors have gained promising progress. In this paper, the merits of combination therapy were analyzed from three aspects:immune checkpoint inhibitors, hyperthermia, hyperthermia combined with immune checkpoint inhibitors, and the future research directions of hyperthermia combined with immune checkpoint inhibitors were prospected.