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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

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.

Related collections

Most cited references 133

Record: found
Abstract: found
Article: not found

The blockade of immune checkpoints in cancer immunotherapy.

Drew M Pardoll (2012)

Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.

0 comments Cited 5137 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer

Hossein Borghaei, Luis Paz-Ares, Leora Horn … (2015)

Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity.

0 comments Cited 2124 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

F. Stephen Hodi, Steven J O'Day, David F McDermott … (2010)

An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab--which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response--administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)

0 comments Cited 2080 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Michele Sommariva:

ORCID: http://orcid.org/0000-0002-7622-0996

michele.sommariva@unimi.it

Journal

Journal ID (nlm-ta): J Exp Clin Cancer Res

Journal ID (iso-abbrev): J Exp Clin Cancer Res

Title: Journal of Experimental & Clinical Cancer Research : CR

Publisher: BioMed Central (London )

ISSN (Print): 0392-9078

ISSN (Electronic): 1756-9966

Publication date (Electronic): 9 November 2020

Publication date PMC-release: 9 November 2020

Publication date Collection: 2020

Volume: 39

Electronic Location Identifier: 236

Affiliations

[1 ]GRID grid.4708.b, ISNI 0000 0004 1757 2822, Dipartimento di Scienze Biomediche per la Salute, , Università degli Studi di Milano, ; via Mangiagalli 31, 20133 Milan, Italy

[2 ]GRID grid.417893.0, ISNI 0000 0001 0807 2568, Molecular Targets Unit, Department of Research, , Fondazione IRCCS – Istituto Nazionale dei Tumori, ; via Amadeo 42, 20133 Milan, Italy

[3 ]GRID grid.417893.0, ISNI 0000 0001 0807 2568, Thoracic Oncology Unit, Medical Oncology Department, , Fondazione IRCCS Istituto Nazionale dei Tumori, ; via Venezian 1, 20133 Milan, Italy

Author information

Michele Sommariva http://orcid.org/0000-0002-7622-0996

Article

Publisher ID: 1721

DOI: 10.1186/s13046-020-01721-9

PMC ID: 7650183

PubMed ID: 33168050

SO-VID: 528d58a6-cc8b-4bce-bf43-ff38c110fc23

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 18 June 2020

Date accepted : 25 September 2020

Funding

Funded by: Fondazione AIRC per la Ricerca sul Cancro

Award ID: 20554

Award Recipient : Michele Sommariva

Custom metadata

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: hyperprogressive disease,immune checkpoint inhibitors,immunotherapy,immune-mediated mechanisms

Data availability:

ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: hyperprogressive disease, immune checkpoint inhibitors, immunotherapy, immune-mediated mechanisms

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

Read this article at

Abstract

Related collections

Cancer Immunotherapy

Most cited references 133

The blockade of immune checkpoints in cancer immunotherapy.

Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer

Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

Author and article information

Contributors

Journal

Affiliations

Author information

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 801

Cited by 27

Most referenced authors 2,640