Immunotherapy in NSCLC patients with brain metastases. Understanding brain tumor microenvironment and dissecting outcomes from immune checkpoint blockade in the clinic [Pre-print]
| Autor: | Vilariño, N, Bruna, J, Nadal, E, Bosch-Barrera, J, Valiente, M, Vilariño, N., Bruna, J., Bosch-Barrera, J., Valiente, M., Nadal, E. |
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| Přispěvatelé: | Government of Catalonia (España), Ministerio de Ciencia, Innovación y Universidades (España) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
lymphocytes Lung Neoplasms medicine.medical_treatment Programmed Cell Death 1 Receptor Brain tumor microglia CD8-Positive T-Lymphocytes Lymphocyte Activation B7-H1 Antigen 03 medical and health sciences angiogenesis 0302 clinical medicine Immune system Antineoplastic Agents Immunological Clinical Trials Phase II as Topic Carcinoma Non-Small-Cell Lung Antineoplastic Combined Chemotherapy Protocols medicine Tumor Microenvironment Animals Humans Radiology Nuclear Medicine and imaging Lung cancer Randomized Controlled Trials as Topic Tumor microenvironment Clinical Trials Phase I as Topic business.industry Brain Neoplasms General Medicine Immunotherapy medicine.disease Immune checkpoint endothelial cells vascular co-option macrophages 030104 developmental biology Oncology Clinical Trials Phase III as Topic Tumor progression 030220 oncology & carcinogenesis Astrocytes Cancer cell Cancer research immunotherapy business |
| Zdroj: | Repisalud Instituto de Salud Carlos III (ISCIII) |
| Popis: | 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+ infiltration were found in brain metastases compared with matched NSCLC primary tumors, suggesting an immunosuppressive microenvironment in the brain. Reactive astrocytes and tumor associated macrophages are paramount in NSCLC brain metastases and play a role in promoting tumor progression and immune evasion. 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. N.Vilarino is supported by a Rio Hortega scholarship (CM19/00245). J. Bruna and E. Nadal received support from the Accio instrumental d'intensificacio de professionals de la salut (SLT008/18/00028 and SLT006/17/00127) of the Department of Health of the Government of Catalonia. We thank CERCA Program/Generalitat de Catalunya for their institutional support and grant 2017SGR448. M.Valiente is a Ramon y Cajal Investigator (RYC-2013-13365) and EMBO YIP (4053) and received support from MINECO-Retos SAF2017-89643-R, Bristol-Myers Squibb-Melanoma Research Alliance Young Investigator Award 2017 (498103), Beug Foundation's Prize for Metastasis Research 2017, Fundacion Ramon Areces (CIVP19S8163), Worldwide Cancer Research (19-0177), Clinic and Laboratory Integration Program CRI Award 2018 (54545), AECC Coordinated Translational Groups 2017 (GCTRA16015SEOA).J. Bosch-Barrera is the recipient of a Grant from the Health Research and Innovation Strategic Plan (SLT006/17/114; PERIS 2016 2020; Pla estrategic de recerca i innovacio en salut; Departament de Salut, Generalitat de Catalunya). No |
| Databáze: | OpenAIRE |
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