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Review
. 2020 Jul 1;44(4):141-148.
doi: 10.7399/fh.11328.

Predictive biomarkers of response to immune checkpoint inhibitors

María Sacramento Díaz-Carrasco  1 , Eva González-Haba  2 , Juana Inés García-Soler  3 , Alberto Espuny-Miró  4
Affiliations
Review

Predictive biomarkers of response to immune checkpoint inhibitors

María Sacramento Díaz-Carrasco et al. Farm Hosp. .

Abstract
in English, Spanish

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 xists 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.

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 revisiones) 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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