Durable benefit and change in TCR clonality with nivolumab in a Lynch syndrome-associated glioma.

Autor:	Cabezas-Camarero S; Medical Oncology Department, Hospital Clínico Universitario San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Calle Profesor Martin Lagos S/N, 28040, Madrid, Spain., Pérez-Alfayate R; Department of Neurosurgery, Instituto de Neurociencias, Hospital Clínico Universitario San Carlos, Madrid, Spain., García-Barberán V; Molecular Oncology Laboratory, Medical Oncology Department, Hospital Clínico Universitario San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain., Polidura MC; Radiology Department, Hospital Clínico Universitario San Carlos, Madrid, Spain., Gómez-Ruiz MN; Radiology Department, Hospital Clínico Universitario San Carlos, Madrid, Spain., Casado-Fariñas I; Pathology Department, Hospital Clínico Universitario San Carlos, Madrid, Spain., Subhi-Issa IA; Pathology Department, Hospital Clínico Universitario San Carlos, Madrid, Spain., Hernández JCP; Pathology Department, Hospital Clínico Universitario San Carlos, Madrid, Spain., Garre P; Molecular Diagnosis Unit, Clinical Chemistry Department, IML, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clinico Universitario San Carlos, Madrid, Spain., Díaz-Millán I; Research Nurse, Medical Oncology Department, Hospital Clínico Universitario San Carlos, Madrid, Spain., Pérez-Segura P; Medical Oncology Department, Hospital Clínico Universitario San Carlos, Instituto de Investigación Sanitaria San Carlos (IdISSC), Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Therapeutic advances in medical oncology [Ther Adv Med Oncol] 2022 Jun 08; Vol. 14, pp. 17588359221100863. Date of Electronic Publication: 2022 Jun 08 (Print Publication: 2022).
DOI:	10.1177/17588359221100863
Abstrakt:	Germline replication-repair deficient (gRRD) gliomas are exceptional events, and only a few of them have been treated with immune checkpoint inhibitors (ICIs). Contrary to sporadic gliomas, where ICIs have failed to show any objective benefit, the very few patients with gRRD gliomas treated with ICIs to date seem to benefit from programmed-death-1 (PD-1) inhibitors, such as nivolumab or pembrolizumab, either in terms of durable responses or in terms of survival. T-cell immunohistochemistry (IHC) and T-cell receptor (TCR) repertoire using high-throughput next-generation sequencing (NGS) with the Oncomine TCR-Beta-SR assay (Thermo Fisher Scientific) were analyzed in pre- and post-nivolumab tumor biopsies obtained from a patient with a Lynch syndrome-associated glioma due to a germline pathogenic hMLH1 mutation. The aim was to describe changes in the T-cell quantity and clonality after treatment with nivolumab to better understand the role of acquired immunity in gRRD gliomas. The patient showed a slow disease progression and overall survival of 10 months since the start of anti-PD-1 therapy with excellent tolerance. A very scant T-cell infiltrate was observed both at initial diagnosis and after four cycles of nivolumab. The drastic change observed in TCR clonality in the post-nivolumab biopsy may be explained by the highly spatial and temporal heterogeneity of glioblastomas. Despite the durable benefit from nivolumab, the scant T-cell infiltrate possibly explains the lack of objective response to anti-PD-1 therapy. The major change in TCR clonality observed after nivolumab possibly reflects the evolving molecular heterogeneity in a highly pre-treated disease. An in-deep review of the available literature regarding the role of ICIs in both sporadic and gRRD gliomas was conducted. Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Santiago Cabezas-Camarero Consultant for: Bristol-Myers Squibb, Merck, MSD. Speaker’s Bureau for: Bristol-Myers Squibb, Merck, MSD. Employee of: None. Grant/Research support from (Clinical Trials): Bristol-Myers Squibb, AstraZeneca, MSD. Travel and Academic work Fees from: Merck, MSD and Bristol-Myers Squibb. Pedro Pérez Segura Consultant for: Bristol-Myers Squibb, Merck, MSD. Speaker’s Bureau for: Bristol-Myers Squibb, Merck, MSD. Employee of: None. Grant/Research support from (Clinical Trials): Bristol-Myers Squibb, AstraZeneca, MSD. Travel and Academic work Fees from: Merck, MSD and Bristol-Myers Squibb. The rest of the authors declare no conflicts of interest relevant to the publication of this article. (© The Author(s), 2022.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu