How can immune checkpoint inhibitors cause hyperprogression in solid tumours?

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INTRODUCTION

Since approval by the Food and Drug Administration (FDA) in 2011 of the first antibody, ipilimumab, targeting an immune checkpoint inhibitors (ICI) (1), this class of inhibitors has rapidly developed to include a large variety of cancer indications. Currently approved agents contribute to the activation of anti-tumor cytotoxic T cells by abrogating the immune checkpoint signaling triggered by tumor cells or microenvironment. Monoclonal antibodies targeting CTLA-4 (ipilimumab), PD-1 (nivolumab, pembrolizumab), and PD-L1 (atezolizumab, avelumab, and durvalumab) are currently approved for the treatment of numerous cancers, however, significant responses to immunotherapy remain restricted to a minority of patients and certain tumor types. Unsuccessful treatment may be due to primary resistance or acquired resistance (2–5). In some cases, the disease develops faster than expected and in a more aggressive manner after immune checkpoint targeting immunotherapy. This phenomenon, designated as hyperprogressive disease (HPD), corresponds to a paradoxical boost in tumor growth under treatment and has been described in non-squamous non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), urothelial bladder carcinoma, hepatocellular carcinoma, gastric cancer, and anorectal melanoma (6–14), with a rate ranging between 4 and 29%. There are currently few data explaining the occurrence of HPD or allowing clinicians to identify patients at risk of developing HPD. The aim of this review is to provide an update about HPD and potential mechanisms explaining how ICI can induce this phenomenon. Denis M Frontiers in Immunology 2020