The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth

Cancer Cell, Год журнала: 2023, Номер 41(3), С. 374 - 403

Опубликована: Март 1, 2023

Язык: Английский

---

Embracing cancer complexity: Hallmarks of systemic disease

Cell, Год журнала: 2024, Номер 187(7), С. 1589 - 1616

Опубликована: Март 1, 2024

Язык: Английский

---

The local microenvironment drives activation of neutrophils in human brain tumors

Cell, Год журнала: 2023, Номер 186(21), С. 4546 - 4566.e27

Опубликована: Сен. 27, 2023

Neutrophils are abundant immune cells in the circulation and frequently infiltrate tumors substantial numbers. However, their precise functions different cancer types remain incompletely understood, including brain microenvironment. We therefore investigated neutrophils tumor tissue of glioma metastasis patients, with matched peripheral blood, herein describe first in-depth analysis neutrophil phenotypes these tissues. Orthogonal profiling strategies humans mice revealed that tumor-associated (TANs) differ significantly from blood have a prolonged lifespan immune-suppressive pro-angiogenic capacity. TANs exhibit distinct inflammatory signature, driven by combination soluble mediators necrosis factor alpha (TNF-ɑ) Ceruloplasmin, which is more pronounced versus glioma. Myeloid cells, macrophages, emerge at core this network pro-inflammatory mediators, supporting concept critical myeloid niche regulating overall suppression human tumors.

Язык: Английский

---

Interrogation of endothelial and mural cells in brain metastasis reveals key immune-regulatory mechanisms

Cancer Cell, Год журнала: 2024, Номер 42(3), С. 378 - 395.e10

Опубликована: Янв. 21, 2024

Brain metastasis (BrM) is a common malignancy, predominantly originating from lung, melanoma, and breast cancers. The vasculature key component of the BrM tumor microenvironment with critical roles in regulating metastatic seeding progression. However, heterogeneity major vascular components, namely endothelial mural cells, still poorly understood. We perform single-cell bulk RNA-sequencing sorted cell types detect multiple subtypes enriched specifically compared to non-tumor brain, including previously unrecognized immune regulatory subtypes. integrate human data mouse models, creating platform interrogate targets for treatment BrM. find that CD276 checkpoint molecule significantly upregulated vasculature, anti-CD276 blocking antibodies prolonged survival preclinical trials. This study provides important insights into complex interactions between cancer translational relevance designing therapeutic interventions.

Язык: Английский

---

Single-cell profiling transcriptomic reveals cellular heterogeneity and cellular crosstalk in breast cancer lymphatic node, bone, and brain metastases

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 17, 2025

Breast cancer is the most common malignant tumor in world, and its metastasis main cause of death breast patients. However, differences between primary tissue lymphatic node, bone, brain metastases at single-cell level are not fully understood. We analyzed microenvironment heterogeneity samples (n = 4), node 3), bone 2) using sequencing data from GEO database. The epithelial cells were characterized by InferCNV algorithm. cell-cell communication was CellChat package. biological function cell subpopulations gene set variation analysis. expression STMN1 immunohistochemical staining. proportion pCAFs explored multispectral identified seven clusters metastatic (Lymphatic brain, metastases) analyzing transcriptomic profiles. T-NK B dominated with metastasis, whereas fibroblasts prevalent cancer. five T (T memory, CD8 + cells, regulatory natural killer CD4 cells), three (naïve memory plasma cancer-associated (CAFs) (Smooth muscle (SMC), pericyte, antigen-presenting CAFs (apCAFs), proliferative (pCAFs), matrix (mCAFs)). Notably. metastasis. Furthermore, we four subpopulations: G0, G1, G2, G3. G2 population exhibited strong invasion ability, it can differentiate into G3 ability proliferation-related G1 after Cell-cell demonstrated an interaction metastasis-associated cells. Finally, discovered that advanced cancer, pCAF increased associated a poor prognosis This study elucidated potential cellular origins drivers to nodes, utilizing prognosis.

Язык: Английский

---

Genomic analysis and clinical correlations of non-small cell lung cancer brain metastasis

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Авг. 17, 2023

Abstract Up to 50% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), yet the study BM genomics has been limited by tissue access, incomplete clinical data, and a lack comparison paired extracranial specimens. Here we report cohort 233 resected sequenced (MSK-IMPACT) NSCLC comprehensive data. With matched samples (47 primary tumor, 42 metastatic), show CDKN2A/B deletions cycle pathway alterations be enriched in samples. Meaningful clinico-genomic correlations are noted, namely EGFR leptomeningeal disease (LMD) MYC amplifications multifocal regional progression. Patients who developed early LMD frequently have had uncommon, multiple, persistently detectable driver mutations. The distinct mutational patterns identified specimens compared other sites suggest specific biologic underpinnings intracranial

Язык: Английский

---

Stereotactic Radiosurgery and Stereotactic Fractionated Radiotherapy in the Management of Brain Metastases

Cancers, Год журнала: 2024, Номер 16(6), С. 1093 - 1093

Опубликована: Март 8, 2024

The management of brain metastases (BM) remains an important and complex issue in the treatment cancer-related neurological complications. BM are particularly common patients diagnosed with lung, melanoma, or breast cancer. Over past decade, therapeutic approaches for majority have changed. Considering addressing fact that living longer, need to provide effective local control while preserving quality life neurocognition is fundamental. SRS SRT become a more commonly chosen option BM. Despite significant advances BM, numerous questions remain regarding patient selection optimal sequencing. Clinical trials critical advancing our understanding especially as alternatives available. Therefore, it imperative interdisciplinary teams improve their latest SRS-SRT. This review aims comprehensively explore treatments covering clinical considerations application (e.g., eligibility), managing limited multiple intact brainstem metastases, exploring combination therapies systemic treatments, considering health economic perspective.

Язык: Английский

---

Embracing diversity: macrophage complexity in cancer

Trends in cancer, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

---

Single-cell atlas of endothelial and mural cells across primary and metastatic brain tumors

Immunity, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

---

NETosis: Sculpting tumor metastasis and immunotherapy

Immunological Reviews, Год журнала: 2023, Номер 321(1), С. 263 - 279

Опубликована: Сен. 15, 2023

Summary The process of neutrophil extracellular traps (NETs) formation, called NETosis, is a peculiar death modality neutrophils, which was first observed as an immune response against bacterial infection. However, recent work has revealed the unique biology NETosis in facilitating tumor metastatic process. Neutrophil released by microenvironment (TME) shield cells from cytotoxic immunity, leading to impaired clearance. Besides, tapped NETs enable travel through vessels and subsequently seed distant organs. Targeted ablation been proven be beneficial potentiating efficacy cancer immunotherapy settings. This review outlines impact at almost all stages metastasis. Furthermore, understanding multifaceted interplay between TME components crucial for supporting rational development highly effective combination immunotherapeutic strategies with anti‐NETosis patients disease.

Язык: Английский

---