Elucidating Sex-Specific Immune Profiles in a Breast Cancer Model DOI Open Access
Ebony Hargrove-Wiley,

Dora Obodo,

Wendy Bindeman

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(23), С. 13113 - 13113

Опубликована: Дек. 6, 2024

Breast cancer is commonly thought of as a "women's disease". However, men are increasingly diagnosed with the disease, and their mortality rates disparately higher than those female patients. The abundance composition immune microenvironment determinants breast progression survival. It well documented that there sex-specific differences in response to several diseases, including various cancers. effects these context remain be explored. This study demonstrates sex hormonal landscape MMTV-PyMT transgenic murine model male ER+ using single-cell RNA sequencing (scRNA-Seq), whole-slide immunohistochemistry, flow cytometry. Mammary tumors mice had increased estrogen receptor alpha expression enriched nuclear binding signatures compared tumors. In tumor compartment, lower intratumoral leukocyte infiltration. Yet, scRNA-Seq analysis reveals more immunostimulatory antitumor populations primary metastatic lungs females. Despite favorable innate profile, burden was mice. Our data support sex-dependent mammary carcinoma associated tumor, likely host, environment. With emerging therapeutics targeting microenvironment, characterizing profiles critical for optimizing use all

Язык: Английский

NFE2-driven neutrophil polarization promotes pancreatic cancer liver metastasis progression DOI

Wenchao Xu,

Jianzhou Liu, Qiaofei Liu

и другие.

Cell Reports, Год журнала: 2025, Номер 44(2), С. 115226 - 115226

Опубликована: Янв. 18, 2025

Язык: Английский

Процитировано

2
Brd7 loss reawakens dormant metastasis initiating cells in lung by forging an immunosuppressive niche DOI Creative Commons
Jayanta Mondal, Junfeng Zhang,

Qing Feng

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Фев. 5, 2025

Metastasis in cancer is influenced by epigenetic factors. Using an vivo screen, we demonstrate that several subunits of the polybromo-associated BAF (PBAF) chromatin remodeling complex, particularly Brd7, are required for maintaining breast metastatic dormancy lungs female mice. Brd7 loss induces reawakening, along with modifications epigenomic landscapes and upregulated oncogenic signaling. Breast cells harboring inactivation also reprogram surrounding immune microenvironment downregulating MHC-1 expression promoting a pro-metastatic cytokine profile. Flow cytometric single-cell analyses reveal increased levels pro-tumorigenic inflammatory transitional neutrophils, CD8+ exhausted T cells, CD4+ stress response from mice Brd7-deficient metastases. Finally, attenuating this immunosuppressive milieu neutrophil depletion, extracellular trap (NET) inhibition, or checkpoint therapy abrogates outgrowth. These findings implicate PBAF triggering outgrowth cancer, pointing to targetable underlying mechanisms involving specific cell compartments. Metastasis-initiating can reawaken dormant state initially allowed them survive, Here, authors show promotes tumor drives reawakening lung.

Язык: Английский

Процитировано

1
TEAD inhibition alters the lung immune microenvironment and attenuates metastasis. DOI Open Access
Raneen Rahhal, Marcel O. Schmidt,

Maha Moussa

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

The Hippo pathway signaling mediated through YAP/TAZ, and the transcription factor TEAD is known to be involved in primary tumor progression. Here we report that novel inhibitors (iTEAD) cause a significant reduction outgrowth of lung metastases from triple negative breast cancer (TNBC) models predominantly changes stromal immune signaling. inhibition did not affect proliferation TNBC cells vitro or growth vivo . In normal mice were treated with iTEAD absence tumors, lungs showed decrease pro-tumor inflammatory pathways. However, IL12 was enhanced its production isolated tissue resident macrophages, but bone marrow derived elevated. syngeneic mouse models, suppressed inflammation M2-like macrophage phenotype tissues, increased infiltration CD8+ T into as well Th1 CD4+ cells, restoring an responsive microenvironment. iTEAD-treated cytotoxicity degranulation when co-cultured via IL-2 activity. Furthermore, knockdown, T-cell crosstalk anti-tumor activity 3D tumorspheres which reversed by neutralizing antibodies. Our data supports multifaceted model on innate adaptive they respond cell signals reveals important could reverse suppression eliminate seeded lungs.

Язык: Английский

Процитировано

0
Single-cell transcriptomic analysis reveals dynamic changes in the liver microenvironment during colorectal cancer metastatic progression DOI Creative Commons
Yue Jiang,

Guojie Long,

Xiaoming Huang

и другие.

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Март 16, 2025

Metastasis is a leading cause of cancer-related deaths, with the liver being most frequent site metastasis in colorectal cancer. Previous studies have predominantly focused on influence primary tumor itself metastasis, relatively limited research examining changes within target organs. Using an orthotopic mouse model cancer, single-cell sequencing was employed to profile transcriptomic landscape pre-metastatic and metastatic livers. The analysis identifying cellular molecular hepatic microenvironment, particular emphasis inflammatory pathways immune cell populations. A neutrophil subpopulation high Prok2 expression identified, showing elevated levels liver. Increased infiltration Prok2⁺ neutrophils correlated poor prognosis cancer patients. In niche (MN), these showed App Cd274 (PD-L1) expression, suppressing macrophage phagocytosis promoting T-cell exhaustion. infiltrated both macro-metastatic environments, potentially driving immunosuppression through inhibition Targeting could represent novel therapeutic strategy for preventing

Язык: Английский

Процитировано

0
Translation dysregulation in cancer as a source for targetable antigens DOI Creative Commons

Chen Weller,

Osnat Bartok,

Christopher S. McGinnis

и другие.

Cancer Cell, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Sequencing of high-frequency mutated genes in breast cancer (BRCA) and associated-functions analysis DOI
Xue‐Lian Li, Mei Yang, Liyuan Yang

и другие.

International Journal of Clinical and Experimental Pathology, Год журнала: 2025, Номер 18(2), С. 46 - 62

Опубликована: Янв. 1, 2025

Mutations or aberrant expression of genes in an organism tend not to be completely random and this cumulative effect predisposes the development malignant tumours. This study aims reveal possible high frequency mutated genes, then investigate their role development, prognosis, signalling pathway function drug resistance breast cancer. The cancer (BRCA) clinical samples were identified detected by high-throughput sequencing. High-frequency mutant counted. Gene profiles relationship with prognosis analysed throughout TCGA database. qRT-PCR was used analyse mRNA levels six high-frequency BRCA tissues cell lines. IHC protein tissues. linear interaction, single-cell layer clustering status influence immune infiltration degree among these bioinformatics analysis. STITCH cMAP datasets for gene interaction networks, association enrichment drug-transcriptome analyses. effects trastuzumab on proliferative capacity cells, as well determined CCK8 assay. that statistically found have mutations recruited present sequencing analysis included TP53, PIK3CA, NF1, TBX3, BRCA1 BRCA2. correlation further demonstrated using database: trend similar TCGA. showed BRCA2 higher tumor than normal samples, opposite a observed expressions displayed same IHC. Other results include 1) single resulted significant few overlapping regions; 2) different degrees infiltration; 3) between each other; 4) network had partially molecules; 5) PI3K key BRCA. Finally, proliferation ability confirmed optimal concentration its genes.

Язык: Английский

Процитировано

0
SLC35A2-mediated bisected GlcNAc-modified extracellular vesicles enhance immune regulation in breast cancer lung metastasis DOI
Yangyang Li, Tao Guo,

Juntong He

и другие.

International Immunopharmacology, Год журнала: 2025, Номер 154, С. 114505 - 114505

Опубликована: Март 31, 2025

Язык: Английский

Процитировано

0
Interrogating the roles of lymph node metastasis in systemic immune surveillance DOI
Pamela A. Basto, Nathan E. Reticker-Flynn

Clinical & Experimental Metastasis, Год журнала: 2024, Номер 41(4), С. 351 - 359

Опубликована: Фев. 5, 2024

Язык: Английский

Процитировано

2
Single-cell analysis of breast cancer metastasis reveals epithelial-mesenchymal plasticity signatures associated with poor outcomes DOI Creative Commons
Juliane Winkler,

Weilun Tan,

Catherine M.M. Diadhiou

и другие.

Journal of Clinical Investigation, Год журнала: 2024, Номер 134(17)

Опубликована: Сен. 2, 2024

Metastasis is the leading cause of cancer-related deaths. It unclear how intratumor heterogeneity (ITH) contributes to metastasis and metastatic cells adapt distant tissue environments. The study these adaptations challenged by limited access patient material a lack experimental models that appropriately recapitulate ITH. To investigate cell contribution ITH metastasis, we analyzed single-cell transcriptomes matched primary tumors metastases from patient-derived xenograft breast cancer. We found profound transcriptional differences between tumor cells. Primary upregulated several metabolic genes, whereas motility pathway genes were in micrometastases, stress response signaling was during progression. Additionally, identified gene signatures associated with increased potential correlated outcomes. Immune-regulatory control pathways enriched poorly tumors, involved epithelial-mesenchymal transition highly tumors. dominated plasticity (EMP), which presented as dynamic continuum intermediate EMP states characterized specific such CRYAB S100A2. Elevated expression an signature worse Our findings inhibition state therapeutic target block metastasis.

Язык: Английский

Процитировано

2
Spatiotemporal lineage tracing reveals the dynamic spatial architecture of tumor growth and metastasis DOI Creative Commons
Matthew G. Jones, Dawei Sun, Kyung Hoi Min

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 24, 2024

ABSTRACT Tumor progression is driven by dynamic interactions between cancer cells and their surrounding microenvironment. Investigating the spatiotemporal evolution of tumors can provide crucial insights into how intrinsic changes within extrinsic alterations in microenvironment cooperate to drive different stages tumor progression. Here, we integrate high-resolution spatial transcriptomics evolving lineage tracing technologies elucidate expansion, plasticity, metastasis co-evolve with microenvironmental remodeling a Kras;p53 -driven mouse model lung adenocarcinoma. We find that rapid expansion contributes hypoxic, immunosuppressive, fibrotic associated emergence pro-metastatic cell states. Furthermore, metastases arise from spatially-confined subclones primary remodel distant metastatic niche fibrotic, collagen-rich Together, present comprehensive dataset integrating assays sequential state structures promote

Язык: Английский

Процитировано

2