Classification of Tumor Immune Microenvironment According to Programmed Death-Ligand 1 Expression and Immune Infiltration Predicts Response to Immunotherapy Plus Chemotherapy in Advanced Patients With NSCLC

Journal of Thoracic Oncology, Journal Year: 2023, Volume and Issue: 18(7), P. 869 - 881

Published: March 21, 2023

According to mechanisms of adaptive immune resistance, tumor microenvironment (TIME) is classified into four types: (1) programmed death-ligand 1 (PD-L1)-negative and tumor-infiltrating lymphocyte (TIL)-negative (type I); (2) PD-L1-positive TIL-positive II); (3) PD-L1-negative III); (4) TIL-negative IV). However, the relationship between TIME classification model immunotherapy efficacy has not been validated by any large-scale randomized controlled clinical trial among patients with advanced NSCLC.On basis RNA-sequencing immunohistochemistry data from ORIENT-11 study, we optimized evaluated its predictive value for plus chemotherapy.PD-L1 mRNA expression score calculated ESTIMATE method were strongest predictors chemotherapy. Therefore, they determined as definition system. When compared combination therapy chemotherapy alone, only type II subpopulation high PD-L1 was significantly associated improved progression-free survival (PFS) (hazard ratio = 0.12, 95% confidence interval: 0.06-0.25, p < 0.001) overall 0.27, 0.13-0.55, 0.001). In group, had a much longer time, even reaching median PFS or survival, but other three subpopulations susceptible having similar PFS. there no marked association outcomes subtypes.Only both infiltration could benefit in first-line treatment NSCLC. For lacking either infiltration, alone might be better option avoid unnecessary toxicities financial burdens.

Language: Английский

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The Use of Iron Oxide Nanoparticles to Reprogram Macrophage Responses and the Immunological Tumor Microenvironment

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: June 9, 2021

The synthesis and functionalization of iron oxide nanoparticles (IONPs) is versatile, which has enhanced the interest in studying them as theranostic agents over recent years. As IONPs begin to be used for different biomedical applications, it important know how they affect immune system its cell types, especially their interaction with macrophages that are involved clearance. How cells respond therapeutic interventions can condition systemic local tissue response, hence, final outcome. Thus, fundamental understand effects have on cancer immunotherapy. biological may result intrinsic features core, inducing reactive oxygen species (ROS) modulating intracellular redox metabolism. Alternatively, driven by nanoparticle coating, example, through membrane receptor engagement. Indeed, exploiting these properties could lead development innovative therapies. In this review, after a presentation elements make up tumor immunological microenvironment, we will review discuss what currently known about immunomodulatory mechanisms triggered IONPs, mainly focusing macrophage polarization reprogramming. Consequently, implications findings context plausible scenarios

Language: Английский

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Tumor Immune Microenvironment and Immunotherapy in Brain Metastasis From Non-Small Cell Lung Cancer

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Feb. 17, 2022

Brain metastasis (BM), a devastating complication of advanced malignancy, has high incidence in non-small cell lung cancer (NSCLC). As novel systemic treatment drugs and improved, more sensitive imaging investigations are performed, patients will be diagnosed with BM. However, the main methods face risk complications at present. Therefore, based on immunotherapy tumor immune microenvironment been proposed. The development NSCLC its BM is closely related to microenvironment, surrounding where cells live. In event BM, metastatic composed extracellular matrix, tissue-resident that change colonization blood-derived cells. Immune-related chemicals brain targeted by immunotherapy, checkpoint inhibition therapy being most important. Blocking immunosuppression targeting checkpoints provides suitable strategy for cancers. past few years, several therapeutic advances have changed outlook from NSCLC. According emerging evidence, plays an essential role treating significant safety profile than others. This article discusses recent biology NSCLC, reviews mechanisms diverse stages, emphasizes metastasis. addition, clinical this disease mentioned.

Language: Английский

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Risk factors for brain metastasis in lung cancer: an umbrella review of systematic reviews and meta-analyses

BMJ Open, Journal Year: 2025, Volume and Issue: 15(1), P. e087181 - e087181

Published: Jan. 1, 2025

Objectives To conduct an umbrella review to extensively evaluate and summarise the evidence regarding relationship between risk factors occurrence of brain metastasis in lung cancer. Design Umbrella systematic reviews meta-analyses. Data sources Four databases (PubMed, EMBASE, Web Science Cochrane Library) were searched from inception 10 November 2024. Eligibility criteria Systematic meta-analyses that assessed cancer included. Only English language studies considered. extraction synthesis Two authors independently extracted data methodological quality bias included studies. Certainty was evaluated summarised for each identified factor. Results Six reviews/meta-analyses The these varied, with most having low or critically quality. Epidermal growth factor receptor mutations, female gender, adenocarcinoma advanced tumour stage associated increased metastasis. Prophylactic cranial irradiation older age reduced risk. Conclusions This suggests several may be cancer, but overall is low. Future improved methodologies are needed validate findings. PROSPERO registration number CRD42023484563

Language: Английский

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Progress in personalized immunotherapy for patients with brain metastasis

npj Precision Oncology, Journal Year: 2025, Volume and Issue: 9(1)

Published: Jan. 29, 2025

Brain metastasis leads to poor outcomes and CNS injury, significantly reducing quality of life survival rates. Advances in understanding the tumor immune microenvironment have revealed promise immunotherapies, which, alongside surgery, chemotherapy, radiation, offer improved for some patients. However, resistance immunotherapy remains a critical challenge. This review explores landscape brain metastases, current therapies, clinical trials, need personalized, biomarker-driven approaches optimize outcomes.

Language: Английский

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Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2044 - 2044

Published: Feb. 7, 2024

Brain metastases represent a significant clinical challenge in the treatment of non-small-cell lung cancer (NSCLC), often leading to severe decline patient prognosis and survival. Recent advances imaging systemic treatments have increased detection rates brain metastases, yet outcomes remain dismal due complexity metastatic tumor microenvironment (TME) lack specific biomarkers for early targeted therapy. The intricate interplay between NSCLC cells surrounding TME is pivotal, influencing progression, immune evasion, response This underscores necessity deeper understanding molecular underpinnings microenvironment, identification actionable that can inform multimodal approaches. goal this review synthesize current insights into elucidate mechanisms metastases. Furthermore, we will explore promising horizon emerging biomarkers, both tissue- liquid-based, hold potential radically transform strategies enhancement outcomes.

Language: Английский

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FGFR1 overexpression in non-small cell lung cancer is mediated by genetic and epigenetic mechanisms and is a determinant of FGFR1 inhibitor response

European Journal of Cancer, Journal Year: 2021, Volume and Issue: 151, P. 136 - 149

Published: May 11, 2021

Amplification of fibroblast growth factor receptor 1 (FGFR1) in non-small cell lung cancer (NSCLC) has been considered as an actionable drug target. However, pan-FGFR tyrosine kinase inhibitors did not demonstrate convincing clinical efficacy FGFR1-amplified NSCLC patients. This study aimed to characterise the molecular context FGFR1 expression and define biomarkers predictive inhibitor response. In this study, 635 samples were characterised for protein by immunohistochemistry copy number gain (CNG) situ hybridisation (n = 298) or DNA microarray 189). gene 369) immune profiles 309) also examined. Furthermore, expression, methylation microRNA data from The Cancer Genome Atlas (TCGA) compared. A panel patient-derived xenograft (PDX) models tested response selective antagonist M6123. minority patients demonstrated CNG (10.5%) increased mRNA (8.7%) (4.4%). correlated weakly with expression. Tumours overexpressing typically devoid driver alterations (e.g. EGFR, KRAS) showed reduced infiltration T-lymphocytes lower PD-L1 Promoter identified regulators other cancers. Finally, PDX demonstrating amplification overexpression sensitive unique features tumours high provide a rationale stratify future trials pathway-targeting agents.

Language: Английский

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The Immune Landscape in Brain Metastasis

Neuro-Oncology, Journal Year: 2024, Volume and Issue: 27(1), P. 50 - 62

Published: Oct. 14, 2024

Abstract The prognosis for patients with brain metastasis remains dismal despite intensive therapy including surgical resection, radiotherapy, chemo-, targeted, and immunotherapy. Thus, there is a high medical need new therapeutic options. Recent advances employing high-throughput spatially resolved single-cell analyses have provided unprecedented insights into the composition phenotypes of diverse immune cells in metastatic brain, revealing unique landscape starkly different from that primary tumors or other sites. This review summarizes current evidence on most prominent niche, along their dynamic interactions tumor each other. As abundant cell types this we explore detail phenotypic heterogeneity functional plasticity tumor-associated macrophages, both resident microglia monocyte-derived as well T-cell compartment. We also preclinical clinical trials evaluating potential targeting microenvironment metastasis. Given substantial highlighting significant role microenvironmental niche pathogenesis, comprehensive understanding key molecular cellular factors within holds great promise developing novel approaches innovative combinatory treatment strategies

Language: Английский

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Neuroinflammatory Gene Expression Analysis Reveals Pathways of Interest as Potential Targets to Improve the Recording Performance of Intracortical Microelectrodes

Cells, Journal Year: 2022, Volume and Issue: 11(15), P. 2348 - 2348

Published: July 30, 2022

Intracortical microelectrodes are a critical component of brain-machine interface (BMI) systems. The recording performance intracortical used for both basic neuroscience research and clinical applications BMIs decreases over time, limiting the utility devices. neuroinflammatory response to microelectrode has been identified as significant contributing factor its performance. Traditionally, pathological assessment limited dozen or so known proteins, only few groups have begun explore changes in gene expression following implantation. Our initial characterization profiles mice implanted with non-functional probes revealed many upregulated genes that could inform future therapeutic targets. Emphasis was placed on most involved multiple innate immune sets, including Cd14, C3, Itgam, Irak4. In previous studies, inhibition Cluster Differentiation 14 (Cd14) improved up two weeks after electrode implantation, suggesting CD14 can be explored potential target. However, all measures improvements signal quality lost statistical significance weeks. Therefore, current study investigated pathway at tissue-microelectrode Cd14−/− understand better how Cd14 connected temporary 2-weeks post-surgery, allowing identification co-therapeutic targets may work synergistically improve

Language: Английский

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The coming of age of liquid biopsy in neuro-oncology

Brain, Journal Year: 2023, Volume and Issue: 146(10), P. 4015 - 4024

Published: June 8, 2023

Abstract The clinical role of liquid biopsy in oncology is growing significantly. In gliomas and other brain tumours, targeted sequencing cell-free DNA (cfDNA) from CSF may help differential diagnosis when surgery not recommended be more representative tumour heterogeneity than surgical specimens, unveiling targetable genetic alterations. Given the invasive nature lumbar puncture to obtain CSF, quantitative analysis cfDNA plasma a lively option for patient follow-up. Confounding factors represented by variations due concomitant pathologies (inflammatory diseases, seizures) or clonal haematopoiesis. Pilot studies suggest that methylome temporary opening blood–brain barrier ultrasound have potential overcome some these limitations. Together with this, an increased understanding mechanisms modulating shedding decrypt meaning kinetics blood CSF.

Language: Английский

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