免疫检查点抑制剂治疗相关超进展的研究现状

Current landscape of hyper-progression on immune checkpoint inhibitor therapy

在多种恶性肿瘤中,免疫检查点抑制剂(ICIs)因临床应用见效显著、治疗应答时间长而成为最有前景的免疫治疗手段之一。与此同时,临床研究发现接受ICIs治疗的患者往往在治疗应答中表现出异质性。越来越多的研究表明,在接受免疫治疗后,部分患者不仅未达到临床获益,反而出现肿瘤进程加速演进,即超进展性疾病(HPD)。HPD已成为患者接受ICIs治疗后进展的新模式。迄今为止,尚未发现可靠的生物学标记物来预测肿瘤在ICIs治疗过程中的加速生长。本文旨在总结目前HPD的定义、相关风险因素、潜在病理生理机制、候选生物学标志物和后续治疗策略。

Immune checkpoint inhibitors(ICIs)appear to be one of the most promising immunotherapies with obvious clinical benefits and durable responses in a variety of malignancies.Meanwhile,a heterogeneity of responses appears in patients receiving ICIs,including hyper-progressive disease(HPD).An increasing number of studies have identified HPD as a paradoxical clinical phenomenon that a small subset of patients experience an accelerated tumor growth rate instead of receiving clinical benefits after immunotherapy.HPD has been recently proposed as a new pattern of progression in patients treated with ICIs.Until now,no reliable biological marker has been found to predict this accelerated tumor growth.The purpose of this paper is to summarize the current definition of HPD,related risk factors,potential pathophysiological mechanisms,candidate biomarkers and follow-up treatment strategies.