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...

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Publicado en:Archives of Pathology & Laboratory Medicine Vol. 142; no. 1; pp. 26 - 35
Autores principales: Marginean, Esmeralda Celia, Melosky, Barbara
Formato: pictorial research systematic review tables/charts Journal Article
Publicado: College of American Pathologists Jan2018
Acceso en línea:Ver este registro en EBSCOhost
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        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
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