Mechanisms of hyperprogressive disease after immune checkpoint inhibitor therapy: what we (don’t) know

Journal of Experimental & Clinical Cancer Research

Nicoletta Gagliano¹  Francesca Arnaboldi¹  Andrea Balsari¹  Simone Camelliti¹  Valentino Le Noci¹  Michele Sommariva¹  Lucia Sfondrini¹  Claudia Moscheni¹  Elda Tagliabue²  Francesca Bianchi²  Marina Chiara Garassino³ 

[1] Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, via Mangiagalli 31, 20133, Milan, Italy;Molecular Targets Unit, Department of Research, Fondazione IRCCS – Istituto Nazionale dei Tumori, via Amadeo 42, 20133, Milan, Italy;Thoracic Oncology Unit, Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, via Venezian 1, 20133, Milan, Italy;

关键词: Hyperprogressive disease;    Immune checkpoint inhibitors;    Immunotherapy;    Immune-mediated mechanisms;   

DOI  :  10.1186/s13046-020-01721-9

来源: Springer

【 摘 要 】

Immune checkpoint inhibitors (ICIs) have made a breakthrough in the treatment of different types of tumors, leading to improvement in survival, even in patients with advanced cancers. Despite the good clinical results, a certain percentage of patients do not respond to this kind of immunotherapy. In addition, in a fraction of nonresponder patients, which can vary from 4 to 29% according to different studies, a paradoxical boost in tumor growth after ICI administration was observed: a completely unpredictable novel pattern of cancer progression defined as hyperprogressive disease. Since this clinical phenomenon has only been recently described, a universally accepted clinical definition is lacking, and major efforts have been made to uncover the biological bases underlying hyperprogressive disease. The lines of research pursued so far have focused their attention on the study of the immune tumor microenvironment or on the analysis of intrinsic genomic characteristics of cancer cells producing data that allowed us to formulate several hypotheses to explain this detrimental effect related to ICI therapy. The aim of this review is to summarize the most important works that, to date, provide important insights that are useful in understanding the mechanistic causes of hyperprogressive disease.

【 授权许可】

CC BY