Immunotherapy in NSCLC patients with brain metastases. Understanding brain tumor microenvironment and dissecting outcomes from immune checkpoint blockade in the clinic.
Animals
Antineoplastic Agents, Immunological
/ administration & dosage
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
B7-H1 Antigen
/ antagonists & inhibitors
Brain Neoplasms
/ drug therapy
CD8-Positive T-Lymphocytes
/ immunology
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Clinical Trials, Phase I as Topic
Clinical Trials, Phase II as Topic
Clinical Trials, Phase III as Topic
Humans
Lung Neoplasms
/ drug therapy
Lymphocyte Activation
Programmed Cell Death 1 Receptor
/ antagonists & inhibitors
Randomized Controlled Trials as Topic
Tumor Microenvironment
/ immunology
Astrocytes
Brain metastases
Macrophages
Non-small-cell lung cancer
PD-L1 expression
Tumor microenvironment
tumor infiltrating lymphocytes (TILs)
Journal
Cancer treatment reviews
ISSN: 1532-1967
Titre abrégé: Cancer Treat Rev
Pays: Netherlands
ID NLM: 7502030
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
12
04
2020
revised:
01
06
2020
accepted:
26
06
2020
pubmed:
19
7
2020
medline:
29
8
2020
entrez:
19
7
2020
Statut:
ppublish
Résumé
Brain metastases are frequent complications in patients with non-small-cell lung cancer (NSCLC) associated with significant morbidity and poor prognosis. Our goal is to give a global overlook on clinical efficacy from immune checkpoint inhibitors in this setting and to review the role of biomarkers and molecular interactions in brain metastases from patients with NSCLC. We reviewed clinical trials reporting clinical outcomes of patients with NSCLC with brain metastases as well as publications assessing the tumor microenvironment and the complex molecular interactions of tumor cells with immune and resident cells in brain metastases from NSCLC biopsies or preclinical models. Although limited data are available on immunotherapy in patients with brain metastases, immune checkpoint inhibitors alone or in combination with chemotherapy have shown promising intracranial efficacy and safety results. The underlying mechanism of action of immune checkpoint inhibitors in the brain niche and their influence on tumor microenvironment are still not known. Lower PD-L1 expression and less T CD8 Discordances in the immune profile between primary tumours and brain metastases underscore differences in the tumour microenvironment and immune system interactions within the lung and brain niche. The characterization of immune phenotype of brain metastases and dissecting the interplay among immune cells and resident stromal cells along with cancer cells is crucial to unravel effective immunotherapeutic approaches in patients with NSCLC and brain metastases.
Sections du résumé
BACKGROUND
BACKGROUND
Brain metastases are frequent complications in patients with non-small-cell lung cancer (NSCLC) associated with significant morbidity and poor prognosis. Our goal is to give a global overlook on clinical efficacy from immune checkpoint inhibitors in this setting and to review the role of biomarkers and molecular interactions in brain metastases from patients with NSCLC.
METHODS
METHODS
We reviewed clinical trials reporting clinical outcomes of patients with NSCLC with brain metastases as well as publications assessing the tumor microenvironment and the complex molecular interactions of tumor cells with immune and resident cells in brain metastases from NSCLC biopsies or preclinical models.
RESULTS
RESULTS
Although limited data are available on immunotherapy in patients with brain metastases, immune checkpoint inhibitors alone or in combination with chemotherapy have shown promising intracranial efficacy and safety results. The underlying mechanism of action of immune checkpoint inhibitors in the brain niche and their influence on tumor microenvironment are still not known. Lower PD-L1 expression and less T CD8
CONCLUSIONS
CONCLUSIONS
Discordances in the immune profile between primary tumours and brain metastases underscore differences in the tumour microenvironment and immune system interactions within the lung and brain niche. The characterization of immune phenotype of brain metastases and dissecting the interplay among immune cells and resident stromal cells along with cancer cells is crucial to unravel effective immunotherapeutic approaches in patients with NSCLC and brain metastases.
Identifiants
pubmed: 32682248
pii: S0305-7372(20)30105-5
doi: 10.1016/j.ctrv.2020.102067
pii:
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
B7-H1 Antigen
0
CD274 protein, human
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
102067Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. E. Nadal has received honoraria for participating in advisory boards from Bristol Myers Squibb, Merck Sharpe & Dohme, Lilly, Roche, Pfizer, Takeda, Boehringer Ingelheim and AstraZeneca. E. Nadal has received research funding from Roche and Pfizer.J. Bosch-Barrera serves on advisory boards and/or accepted honoraria for giving lectures from Bristol Myers-Squibb (BMS), Roche, Merck Sharp & Dohme (MSD), AstraZeneca, Novartis and Boehringer-Ingelheim. J. Bosch-Barrera has also received grants for research from Pfizer and Roche. All remaining authors have declared no conflicts of interest.