[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-331293-105":59,"doc-detail-331293-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","proteomic-investigation-of-immune-checkpoints-and-some-of-their-inhibitors","Proteomic Investigation of Immune Checkpoints and Some of Their Inhibitors","","Immune checkpoints are key molecules that regulate antitumor immune responses by transmitting inhibitory or stimulatory signals through receptor–ligand interactions. Over the last decade, checkpoint inhibitors targeting CTLA-4, PD-1, and PD-L1 have become central to immune therapy, improving outcomes for some cancers but with limited overall response rates. Although many patients initially respond, acquired resistance and disease progression can occur, lowering durability. In clinical practice, inhibitors are used alone or combined with chemotherapy across numerous cancer types. Major challenges include clarifying resistance mechanisms, discovering more effective inhibitors, broadening benefit to more patients, managing immune-related adverse effects, and identifying predictive biomarkers. The work also considers treatment affordability and emphasizes the role of mass spectrometry-based proteomic analyses in studying checkpoint biology and inhibitor development.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/proteomic-investigation-of-immune-checkpoints-and-some-of-their-inhibitors/331293/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/proteomic-investigation-of-immune-checkpoints-and-some-of-their-inhibitors/331293.png","ImageObject",300,407,{"name":92,"@type":93},"Levi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role do immune checkpoints play in antitumor immunity?","Question",{"text":112,"@type":113},"Immune checkpoints are crucial molecules that help maintain antitumor immune responses by generating inhibitory or stimulatory signals based on receptor–ligand interactions.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why is immune checkpoint therapy important and what limitation does it face?",{"text":117,"@type":113},"Checkpoint inhibitors have become a leading immune therapy approach, but the medium overall response rate remains relatively poor and durable responses occur only for subsets of patients.",{"name":119,"@type":110,"acceptedAnswer":120},"What challenges must be addressed to improve immune checkpoint therapy outcomes?",{"text":121,"@type":113},"Key challenges include understanding resistance mechanisms, identifying more efficient inhibitors, extending benefits to more patients, managing immune-related adverse effects, and urgently finding biomarkers to predict positive responders.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},331293,1790976541,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},7971461740909,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Review  \nProteomic Investigation of Immune Checkpoints and Some of Their Inhibitors  \nMarco Agostini , Pietro Traldi * and Mahmoud Hamdan  \nCitation: Agostini, M.; Traldi, P.; Hamdan, M. Proteomic Investigation of Immune Checkpoints and Some of Their Inhibitors. Int. J. Mol. Sci. 2024, 25, 9276. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms25179276  \nAcademic Editor: Leo Kei Iwai  \nReceived: 23 May 2024  \nRevised: 19 August 2024  \nAccepted: 21 August 2024  \nPublished: 27 August 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nIstituto di Ricerca Pediatrica Città della Speranza, Corso Stati Uniti 4, 35100 Padova, Italy;  \n[m.agostini@unipd.it](m.agostini@unipd.it) (M.A.); [mhglaxo@gmail.com](mhglaxo@gmail.com) (M.H.)  \n* [Correspondence: p.traldi@irpcds.org](Correspondence: p.traldi@irpcds.org)  \nAbstract: Immune checkpoints are crucial molecules for the maintenance of antitumor immune responses. The activation or inhibition of these molecules is dependent on the interactions between receptors and ligands; such interactions can provide inhibitory or stimulatory signals to the various components of the immune system. Over the last 10 years, the inhibition of immune checkpoints, such as cytotoxic T lymphocyte antigen-4, programmed cell death-1, and programmed cell death ligand-1, has taken a leading role in immune therapy. This relatively recent therapy regime is based on the use of checkpoint inhibitors, which enhance the immune response towards various forms of cancer. Fora subset of patients with specific forms of cancer, these inhibitors can induce a durable response to therapy; however, the medium response rate to such therapy remains relatively poor. Recent research activities have demonstrated that the disease response to this highly promising therapy resembles the response of many forms of cancer to chemotherapy, where an encouraging initial response is followed by acquired resistance to treatment and progress of the disease. That said, these inhibitors are now used as single agents or in combination with chemotherapies as first or second lines of treatment for about 50 types of cancer. The prevailing opinion regarding immune therapy suggests that for this approach of therapy to deliver on its promise, a number of challenges have to be circumvented. These challenges include understanding the resistance mechanisms to immune checkpoint blockade, the identification of more efficient inhibitors, extending their therapeutic benefits to a wider audience of cancer patients, better management of immune-related adverse side effects, and, more urgently the identification of biomarkers, which would help treating oncologists in the identification of patients who are likely to respond positively to the immune therapies and, last but not least, the prices of therapy which can be afforded by the highest number of patients. Numerous studies have demonstrated that understanding the interaction between these checkpoints and the immune system is essential for the development of efficient checkpoint inhibitors and improved immune therapies. In the present text, we discuss some of these checkpoints, their inhibitors, and some works in which mass spectrometry-based proteomic analyses were applied.  \nKeywords: proteomic investigations; immune checkpoints; immune system; immune therapy checkpoint inhibitors/therapies; post-translational modifications (PTMs)  \n1. Introduction  \nFrequent genetic and epigenetic alterations that are intrinsic to most cancer cells produce a high number of tumor-associated antigens/proteins that the host’s immune system can recognize. Such recognition induces tumors ","cbCaiaD6Kk604w2D","https://ap.wps.com/l/cbCaiaD6Kk604w2D","pdf",4464186,18,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What role do immune checkpoints play in antitumor immunity?\",\"answer\":\"Immune checkpoints are crucial molecules that help maintain antitumor immune responses by generating inhibitory or stimulatory signals based on receptor–ligand interactions.\"},{\"question\":\"Why is immune checkpoint therapy important and what limitation does it face?\",\"answer\":\"Checkpoint inhibitors have become a leading immune therapy approach, but the medium overall response rate remains relatively poor and durable responses occur only for subsets of patients.\"},{\"question\":\"What challenges must be addressed to improve immune checkpoint therapy outcomes?\",\"answer\":\"Key challenges include understanding resistance mechanisms, identifying more efficient inhibitors, extending benefits to more patients, managing immune-related adverse effects, and urgently finding biomarkers to predict positive responders.\"}]","Proteomic Investigation of Immune Checkpoints and Some of Their Inhibitors | PDF",1789992561,45]