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      Predictive biomarkers of response to immune checkpoint inhibitors Translated title: Biomarcadores predictivos de respuesta a los inhibidores de los puntos de control inmunitario

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          Abstract

          Abstract Objective: The present paper provides a literature review aimed at identifying the tumor-dependent factors capable of influencing a subject's response to immune checkpoint inhibitors, with a special emphasis on those that may act as predictive biomarkers. Method: A search was performed of the terms biomarkers, PD-1, PD-L1, CTLA-4, and checkpoint inhibitors in the title and the abstract of the records in the PubMed database. Articles including relevant information on the tumor-dependent factors capable of influencing a subject's response of immune checkpoint inhibitors were selected. Priority was given to studies in humans (clinical trials and reviews) published between January 2015 and June 2019, in English and Spanish. Results: The literature review exposed the complex relationship that exists between the immune system and tumors. It also revealed that the factors capable of influencing a subject's response to immune checkpoint inhibitors are multiple, heterogeneous and ill understood, which makes it difficult to obtain simple and/or universal predictive biomarkers. Conclusions: The only biomarkers currently used in clinical practice include the expression of the programmed cell death ligand-1 and microsatellite instability/ deficient DNA mismatch repair, but their usefulness is limited. Tumor mutational burden and gene signatures associated to IFN-γ could become useful biomarkers once determination techniques and cutoff points are systematized.

          Translated abstract

          Resumen Objetivo: El objetivo del presente trabajo es identificar mediante revisión bibliográfica los factores dependientes del tumor que condicionan la respuesta a los inhibidores de los puntos de control inmunitario, incidiendo especialmente en aquellos que se postulan como posibles biomarcadores predictivos. Método: Búsquedas en Pubmed con los términos biomarkers, PD-1, PD-L1, CTLA-4, checkpoint inhibitors, en el título o el abstract, seleccionando aquellos que incluyeran información relevante sobre factores tumorales que condicionan la respuesta a los inhibidores de los puntos de control inmunitario. Se priorizaron estudios en humanos (ensayos clínicos y revisions) publicados entre enero de 2015 y junio de 2019, en idiomas inglés y español. Resultados: La revisión pone de manifiesto las complejas relaciones entre sistema inmunitario y tumor, con factores que influyen en la respuesta a los inhibidores de los puntos de control inmunitario variados, y aun poco conocidos, lo cual dificulta la obtención de biomarcadores predictivos sencillos y/o universales. Conclusiones: Actualmente los únicos biomarcadores utilizados en práctica clínica, en algunos escenarios, son la expresión del ligando del receptor de muerte celular programada-1 y la inestabilidad de microsatélites/deficiencias en las enzimas de reparación de los apareamientos erróneos durante la replicación del ácido desoxirribonucleico, aunque su utilidad es limitada. La carga mutacional y las firmas génicas asociadas a interferón gamma se postulan como biomarcadores útiles, una vez sistematizadas las técnicas de determinación y los puntos de corte.

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          Author and article information

          Journal
          fh
          Farmacia Hospitalaria
          Farm Hosp.
          Grupo Aula Médica (Toledo, Toledo, Spain )
          1130-6343
          2171-8695
          August 2020
          : 44
          : 4
          : 141-148
          Affiliations
          [2] Madrid orgnameHospital General Universitario Gregorio Marañón orgdiv1Department of Pharmacy Spain
          [1] El Palmar Murcia orgnameHospital Clínico Universitario Virgen de la Arrixaca orgdiv1Department of Pharmacy Spain
          Article
          S1130-63432020000400005 S1130-6343(20)04400400005
          10.7399/fh.11328
          32646345
          46d538fe-4a3e-453d-8fcd-c5f8cf1c23ce

          This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

          History
          : 29 January 2020
          : 17 June 2019
          Page count
          Figures: 0, Tables: 0, Equations: 0, References: 50, Pages: 8
          Product

          SciELO Spain

          Categories
          Reviews

          Inmunoterapia,Inhibidores puntos de control inmunitario,Biomarcadores,Receptor de muerte celular programada-1,Immunotherapy,Immune checkpoint inhibitors,Programmed cell death-1 receptor,Biomarkers

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