Dormancy and NKG2D system in brain�metastases: Analysis of immunogenicity

Flüh, Charlotte; Mafael, Victor; Adamski, Vivian; Synowitz, Michael; Held‐Feindt, Janka

doi:10.3892/ijmm.2019.4449

Cited by 6 publications

(3 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, studies in brain tumours revealed the role of B7-H3 in regulating cancer stemness and metabolism [49]. As the pathogenesis of BrM involves brain metastatic cells undergoing cycles of dormancy, neural microenvironment adaptation, and brain invasion [50,51], it is possible that B7-H3 may be involved in these mechanisms for cells originating in the breast.…”

Section: Discussionmentioning

confidence: 99%

B7-H3 Expression in Breast Cancer and Brain Metastasis

Joshi,

Beecher,

Lim

et al. 2024

IJMS

View full text Add to dashboard Cite

Brain metastasis is a significant challenge for some breast cancer patients, marked by its aggressive nature, limited treatment options, and poor clinical outcomes. Immunotherapies have emerged as a promising avenue for brain metastasis treatment. B7-H3 (CD276) is an immune checkpoint molecule involved in T cell suppression, which is associated with poor survival in cancer patients. Given the increasing number of clinical trials using B7-H3 targeting CAR T cell therapies, we examined B7-H3 expression across breast cancer subtypes and in breast cancer brain metastases to assess its potential as an interventional target. B7-H3 expression was investigated using immunohistochemistry on tissue microarrays of three clinical cohorts: (i) unselected primary breast cancers (n = 347); (ii) brain metastatic breast cancers (n = 61) and breast cancer brain metastases (n = 80, including a subset of 53 patient-matched breast and brain metastasis cases); and (iii) mixed brain metastases from a range of primary tumours (n = 137). In primary breast cancers, B7-H3 expression significantly correlated with higher tumour grades and aggressive breast cancer subtypes, as well as poorer 5-year survival outcomes. Subcellular localisation of B7-H3 impacted breast cancer-specific survival, with cytoplasmic staining also correlating with a poorer outcome. Its expression was frequently detected in brain metastases from breast cancers, with up to 90% expressing B7-H3. However, not all brain metastases showed high levels of expression, with those from colorectal and renal tumours showing a low frequency of B7-H3 expression (0/14 and 2/16, respectively). The prevalence of B7-H3 expression in breast cancers and breast cancer brain metastases indicates potential opportunities for B7-H3 targeted therapies in breast cancer management.

show abstract

Section: Discussionmentioning

confidence: 99%

B7-H3 Expression in Breast Cancer and Brain Metastasis

Joshi,

Beecher,

Lim

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…In glioblastoma, major histocompatibility complex class I molecules expressed on tumor cells bind to NK cell inhibitory receptors and suppress their immune function 37 , 38 . Gliomas and brain metastases can further downregulate the expression of activating receptors, such as NK Group 2 member D (NKG2D), to evade immune activation of host NK cells 39 , 40 . The tumor microenvironment in pediatric solid tumors is rich in immunosuppressive molecules such as transforming growth factor beta (TGFβ) 41 , 42 , adenosine 43 , PGE2 44 , as well as indoleamine 2,3-dioxygenase (IDO) 45 .…”

Section: Nk Cells In the Brain Tumor Microenvironmentmentioning

confidence: 99%

Advances in NK cell therapy for brain tumors

et al. 2023

View full text Add to dashboard Cite

Despite advances in treatment regimens that comprise surgery, chemotherapy, and radiation, outcome of many brain tumors remains dismal, more so when they recur. The proximity of brain tumors to delicate neural structures often precludes complete surgical resection. Toxicity and long-term side effects of systemic therapy remain a concern. Novel therapies are warranted. The field of NK cell-based cancer therapy has grown exponentially and currently constitutes a major area of immunotherapy innovation. This provides a new avenue for the treatment of cancerous lesions in the brain. In this review, we explore the mechanisms by which the brain tumor microenvironment suppresses NK cell mediated tumor control, and the methods being used to create NK cell products that subvert immune suppression. We discuss the pre-clinical studies evaluating NK cell-based immunotherapies that target several neuro-malignancies and highlight advances in molecular imaging of NK cells that allow monitoring of NK cell-based therapeutics. We review current and ongoing NK cell based clinical trials in neuro-oncology.

show abstract

“…Interestingly, NK cells can also provide a variety of cytokines (e.g., CXCL10) that enhance the aforementioned ability of CD8 and CD4 lymphocytes to induce dormancy in a model of acute myeloid leukemia (AML)( Saudemont et al, 2005 ), however, this study shows only correlation of NK ligand expression with dormancy markers in dormant tumor masses without showing function of NK. Additionally, a recent study showed co-localization of dormancy markers (e.g., H2BK or PDGFB) with ligands of the NK group 2 member D receptor (MICA, MICB, or ULBP1 and 2) in patients with brain metastasis from lung and breast cancers, suggesting that these mechanisms may co-operate in maintaining metastatic dormancy ( Fluh et al, 2020 ).…”

Section: Microenvironmental Regulation Of Dtc Dormancymentioning

confidence: 99%

Could Extracellular Vesicles Contribute to Generation or Awakening of “Sleepy” Metastatic Niches?

Hernández-Barranco

Peinado

2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Pre-metastatic niches provide favorable conditions for tumor cells to disseminate, home to and grow in otherwise unfamiliar and distal microenvironments. Tumor-derived extracellular vesicles are now recognized as carriers of key messengers secreted by primary tumors, signals that induce the formation of pre-metastatic niches. Recent evidence suggests that tumor cells can disseminate from the very earliest stages of primary tumor development. However, once they reach distal sites, tumor cells can persist in a dormant state for long periods of time until their growth is reactivated and they produce metastatic lesions. In this new scenario, the question arises as to whether extracellular vesicles could influence the formation of these metastatic niches with dormant tumor cells? (here defined as “sleepy niches”). If so, what are the molecular mechanisms involved? In this perspective-review article, we discuss the possible influence of extracellular vesicles in early metastatic dissemination and whether they might play a role in tumor cell dormancy. In addition, we comment whether extracellular vesicle-mediated signals may be involved in tumor cell awakening, considering the possibility that extracellular vesicles might serve as biomarkers to detect early metastasis and/or minimal residual disease (MRD) monitoring.

show abstract

Dormancy and NKG2D system in brain�metastases: Analysis of immunogenicity

Cited by 6 publications

References 72 publications

B7-H3 Expression in Breast Cancer and Brain Metastasis

B7-H3 Expression in Breast Cancer and Brain Metastasis

Advances in NK cell therapy for brain tumors

Could Extracellular Vesicles Contribute to Generation or Awakening of “Sleepy” Metastatic Niches?

Contact Info

Product

Resources

About