The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature

Frontiers in Immunology

Immunology

Albina Fejza¹  Evelina Poletto²  Giorgia Schinello²  Emanuele Di Siena²  Greta Carobolante²  Lucrezia Camicia²  Maurizio Mongiat²  Eva Andreuzzi³  Giuseppe Ricci⁴ 

[1] Department of Biochemistry, Faculty of Medical Sciences, UBT-Higher Education Institute, Prishtina, Kosovo;Department of Research and Diagnosis, Division of Molecular Oncology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy;Obstetrics and Gynecology, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy;Obstetrics and Gynecology, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy;Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy;

关键词: extracellular matrix;    cancer;    immune checkpoint inhibitors;    pediatric cancer;    gynecological cancer;    gastrointestinal cancer;    melanoma;    breast cancer;   

DOI  :  10.3389/fimmu.2023.1270981

 received in 2023-08-01, accepted in 2023-09-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionImmune-checkpoint inhibitors (ICIs) have emerged as a core pillar of cancer therapy as single agents or in combination regimens both in adults and children. Unfortunately, ICIs provide a long-lasting therapeutic effect in only one third of the patients. Thus, the search for predictive biomarkers of responsiveness to ICIs remains an urgent clinical need. The efficacy of ICIs treatments is strongly affected not only by the specific characteristics of cancer cells and the levels of immune checkpoint ligands, but also by other components of the tumor microenvironment, among which the extracellular matrix (ECM) is emerging as key player. With the aim to comprehensively describe the relation between ECM and ICIs’ efficacy in cancer patients, the present review systematically evaluated the current literature regarding ECM remodeling in association with immunotherapeutic approaches.MethodsThis review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and was registered at the International Prospective Register of Systematic Reviews (PROSPERO, CRD42022351180). PubMed, Web of Science, and Scopus databases were comprehensively searched from inception to January 2023. Titles, abstracts and full text screening was performed to exclude non eligible articles. The risk of bias was assessed using the QUADAS-2 tool.ResultsAfter employing relevant MeSH and key terms, we identified a total of 5070 studies. Among them, 2540 duplicates, 1521 reviews or commentaries were found and excluded. Following title and abstract screening, the full text was analyzed, and 47 studies meeting the eligibility criteria were retained. The studies included in this systematic review comprehensively recapitulate the latest observations associating changes of the ECM composition following remodeling with the traits of the tumor immune cell infiltration. The present study provides for the first time a broad view of the tight association between ECM molecules and ICIs efficacy in different tumor types, highlighting the importance of ECM-derived proteolytic products as promising liquid biopsy-based biomarkers to predict the efficacy of ICIs.ConclusionECM remodeling has an important impact on the immune traits of different tumor types. Increasing evidence pinpoint at ECM-derived molecules as putative biomarkers to identify the patients that would most likely benefit from ICIs treatments.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351180, identifier CRD42022351180.

【 授权许可】

Unknown   
Copyright © 2023 Fejza, Carobolante, Poletto, Camicia, Schinello, Di Siena, Ricci, Mongiat and Andreuzzi