Kocikowski Mikolaj, Dziubek Katarzyna, Parys Maciej
International Centre for Cancer Vaccine Science, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland.
The Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK.
Cancers (Basel). 2020 Mar 27;12(4):804. doi: 10.3390/cancers12040804.
Immune evasion is a major challenge for the development of successful cancer treatments. One of the known mechanisms is the expression of immune checkpoints (ICs)-proteins regulating the immune cells activation. The advent of immunotherapy using monoclonal antibodies (mAbs) to block the immune checkpoint receptor-ligand interaction brought about a landslide improvement in the treatment responses, leading to a prompt approval of such therapeutics. In recent years, it was discovered that a subset of patients receiving IC blockade treatment experienced a previously unknown pattern of treatment response called hyperprogression (HP), characterised by rapid deterioration on initialisation of the therapy. HP represents an urgent issue for clinicians and drug developers, while posing questions about the adequacy of the current clinical trial process. Here, we briefly summarise the state of knowledge and propose new directions for research into HP mechanisms, focusing on tumour-intrinsic signalling of IC proteins malignantly expressed by cancer. We also discuss the potential role of spontaneously occurring canine cancer in the assessment of immunotherapeutics, which can provide the missing link between murine and human studies.
免疫逃逸是成功开发癌症治疗方法的一项重大挑战。已知机制之一是免疫检查点（ICs）的表达，免疫检查点是调节免疫细胞激活的蛋白质。使用单克隆抗体（mAb）阻断免疫检查点受体-配体相互作用的免疫疗法的出现，使治疗反应得到了巨大改善，从而使此类疗法迅速获得批准。近年来，发现一部分接受IC阻断治疗的患者经历了一种以前未知的治疗反应模式，称为超进展（HP），其特征是在治疗开始后迅速恶化。HP对临床医生和药物开发者来说是一个紧迫问题，同时也对当前临床试验过程的充分性提出了质疑。在此，我们简要总结了相关知识现状，并提出了研究HP机制的新方向，重点关注癌症恶性表达的IC蛋白的肿瘤内在信号传导。我们还讨论了自发性犬类癌症在免疫治疗评估中的潜在作用，它可以提供小鼠研究和人类研究之间缺失的环节。
