Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part II--The Challenge of Programmed Death Ligand-1 Testing and Its Role in Microsatellite Instability-High Colorectal Cancer.
Context.--The world of oncology has changed dramatically in the past few years with the introduction of checkpoint inhibitors and immunotherapy. The promising findings of a small, phase 2 clinical trial that led to the US Food and Drug Administration breakthrough designation and approval of the anti...
| Publicado en: | Archives of Pathology & Laboratory Medicine Vol. 142; no. 1; pp. 26 - 35 |
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| Autores principales: | , |
| Formato: | pictorial research systematic review tables/charts Journal Article |
| Publicado: |
College of American Pathologists
Jan2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=126986878&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 126986878 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00039985 1FS jtl: Archives of Pathology & Laboratory Medicine issn: 00039985 maglogo: N pubinfo: dt: Jan2018 vid: 142 iid: 1 pid: 2550 pub: College of American Pathologists place: Northfield, Illinois artinfo: ui: 126986878 126986878 126986878 10.5858/arpa.2017-0041-RA 126986878 ppf: 26 ppct: 9 formats: fmt: @attributes: type: P tig: atl: Is There a Role for Programmed Death Ligand-1 Testing and Immunotherapy in Colorectal Cancer With Microsatellite Instability? Part II--The Challenge of Programmed Death Ligand-1 Testing and Its Role in Microsatellite Instability-High Colorectal Cancer. aug: au: Marginean, Esmeralda Celia Melosky, Barbara affil: Department of Pathology, University of Ottawa, Ottawa, Ontario, Canada sug: subj: Colorectal Neoplasms Therapy Mutation Immunotherapy Antigens, CD4 Colorectal Neoplasms Diagnosis Colorectal Neoplasms Immunology PubMed Molecular Biology Immunohistochemistry Gene Expression Colorectal Neoplasms Drug Therapy Antineoplastic Agents Therapeutic Use Human Systematic Review ab: Context.--The world of oncology has changed dramatically in the past few years with the introduction of checkpoint inhibitors and immunotherapy. The promising findings of a small, phase 2 clinical trial that led to the US Food and Drug Administration breakthrough designation and approval of the anti--programmed death receptor-1 (PD-1) drug pembrolizumab (Keytruda, Merck, Kenilworth, New Jersey) to treat metastatic/refractory microsatellite instability--high colorectal cancer (CRC) has significantly boosted interest in immunomodulatory therapies in microsatellite instability--high CRC. Objectives.--To review the immune response to cancer and the role of immune checkpoints, focusing on the technical and interpretation challenges of PD-1/programmed death ligand-1 (PD-L1) testing by pathologists and the clinical implications of the test and the therapeutic potential of treating CRC with checkpoint inhibitors. Data Sources.--A PubMed review was performed of articles pertaining to CRC, microsatellite instability and mismatch repair systems, molecular classification, immune response, PD-1/PD-L1, and immunotherapy. Conclusions.--Exciting success with anti--PD-1/PD-L1 and anticytotoxic T-lymphocyte--associated protein 4 (CTLA4) checkpoint inhibitors has already been reported in melanoma and in lung and renal carcinomas. Recently, microsatellite instability--high CRCs, expressing PD-L1 by immunohistochemistry, regardless of the level of that PD-L1 expression, appeared to respond to checkpoint block- ades with anti--PD-1 or anti--PD-L1 agents, whereas microsatellite-stable tumors were much less responsive. With microsatellite instability routinely tested by most centers, studies that include larger cohorts are required to study the predictive role of PD-1/PD-L1 expression in microsatellite instability--high CRC, to assess which immunohistochemistry antibodies to use, to refine the scoring criteria, and to critically analyze the interpretation pitfalls. pubtype: Academic Journal doctype: pictorial research systematic review tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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