Androgen deprivation therapy-resistant club cells are linked to myeloid cell-driven immunosuppression in the prostate tumor microenvironment DOI Open Access
Antti Kiviaho, Sini K. Eerola, Heini Kallio

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 28, 2024

Abstract Prostate cancer treatment resistance is a significant challenge facing the field. Genomic and transcriptomic profiling have partially elucidated mechanisms through which cells escape treatment, but their relation toward tumor microenvironment (TME) remains elusive. Here we present comprehensive landscape of prostate TME at multiple points in standard timeline employing single-cell RNA-sequencing spatial transcriptomics data from 110 patients. We identify club-like as key epithelial cell subtype that acts an interface between immune system. Tissue areas enriched with depleted androgen signaling upregulated expression luminal progenitor markers. Club-like display senescence-associated secretory phenotype presence linked to increased polymorphonuclear myeloid-derived suppressor (PMN-MDSC) activity. Our results indicate partake inducing myeloid inflammation previously associated deprivation therapy resistance, providing rationale for therapeutic targeting.

Language: Английский

Integration Analysis of Single‐Cell Multi‐Omics Reveals Prostate Cancer Heterogeneity DOI Creative Commons

Xiaojie Bian,

Wenfeng Wang, Mierxiati Abudurexiti

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(18)

Published: March 14, 2024

Abstract Prostate cancer (PCa) is an extensive heterogeneous disease with a complex cellular ecosystem in the tumor microenvironment (TME). However, manner which heterogeneity shaped by tumors and stromal cells, or vice versa, remains poorly understood. In this study, single‐cell RNA sequencing, spatial transcriptomics, bulk ATAC‐sequence are integrated from series of patients PCa healthy controls. A stemness subset club cells marked SOX9 high AR low expression identified, markedly enriched after neoadjuvant androgen‐deprivation therapy (ADT). Furthermore, CD8 + CXCR6 T that function as effector reduced malignant PCa. For transcriptome analysis, machine learning computational intelligence comprehensively utilized to identify diversity prostate cell‐cell communication situ. Macrophage neutrophil state transitions along trajectory progression also examined. Finally, immunosuppressive advanced found be associated infiltration regulatory (Tregs), potentially induced FAP fibroblast subset. summary, delineated stage‐specific at resolution, uncovering their reciprocal crosstalk progression, can helpful promoting diagnosis therapy.

Language: Английский

Citations

27
Spatial multi-omics: deciphering technological landscape of integration of multi-omics and its applications DOI Creative Commons

Xiaojie Liu,

Ting Peng,

Miaochun Xu

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Aug. 24, 2024

The emergence of spatial multi-omics has helped address the limitations single-cell sequencing, which often leads to loss context among cell populations. Integrated analysis genome, transcriptome, proteome, metabolome, and epigenome enhanced our understanding biology molecular basis human diseases. Moreover, this approach offers profound insights into interactions between intracellular intercellular mechanisms involved in development, physiology, pathogenesis In comprehensive review, we examine current advancements technologies, focusing on their evolution refinement over past decade, including improvements throughput resolution, modality integration, accuracy. We also discuss pivotal contributions revealing heterogeneity, constructing detailed atlases, deciphering crosstalk tumor immunology, advancing translational research cancer therapy through precise mapping.

Language: Английский

Citations

18
Linking Metastatic Behavior and Metabolic Heterogeneity of Circulating Tumor Cells at Single‐Cell Level Using an Integrative Microfluidic System DOI Creative Commons
Ying Hou, Jiaxu Lin,

Hongren Yao

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Abstract Circulating tumor cells (CTCs) are pivotal biomarkers in metastasis, however, the underlying molecular mechanism of CTCs behavioral heterogeneity during metastasis remains unexplored. Here, an integrative workflow is developed to link behavior characteristics metabolic profiling within individual CTCs, which simulates metastatic process on a microfluidic system and combined with single‐cell mass spectrometry (MS) detection. Spheroid‐derived HCT116 tracked extracted via temporary vascular system, revealing various arrest patterns under biomimetic shear flow. Downstream MS analysis characterizes 17 cellular metabolites associates profiles de‐adhesion behaviors same identifying potential high‐metastatic subpopulation enhanced ability evaluating critical involved pathways. Additionally, metastasis‐inhibiting effect anti‐tumor drug 5‐fluorouracil by reducing spheroids elucidated. This approach offers valuable opportunity dissect interplay foster insights into mechanisms phenotypes process.

Language: Английский

Citations

2
Prostate cancer microenvironment: multidimensional regulation of immune cells, vascular system, stromal cells, and microbiota DOI Creative Commons
Lin Chen, Yuxin Xu,

Yuanshuo Wang

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Oct. 12, 2024

Prostate cancer (PCa) is one of the most prevalent malignancies in males worldwide. Increasing research attention has focused on PCa microenvironment, which plays a crucial role tumor progression and therapy resistance. This review aims to provide comprehensive overview key components including immune cells, vascular systems, stromal microbiota, explore their implications for diagnosis treatment. Keywords such as "prostate cancer", "tumor microenvironment", "immune cells", "vascular system", "stromal "microbiota" were used literature retrieval through online databases PubMed Web Science. Studies related microenvironment selected, with particular focus those discussing roles microbiota development, progression, treatment PCa. The selection criteria prioritized peer-reviewed articles published last five years, aiming summarize analyze latest advancements clinical relevance regarding microenvironment. highly complex dynamic, cells contributing immunosuppressive conditions, promoting growth, potentially affecting androgen metabolism. Vascular systems support angiogenesis, fosters expansion. Understanding these offers insight into mechanisms driving opens avenues novel therapeutic strategies targeting A deeper understanding advancing diagnostic techniques developing precision therapies. highlights potential improve patient outcomes, emphasizing its significance broader context innovation.

Language: Английский

Citations

12
CXCL14 in prostate cancer: complex interactions in the tumor microenvironment and future prospects DOI Creative Commons
Lei Tang, Xin Chen, Jianquan Hou

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 4, 2025

CXCL14 is a highly conserved chemokine expressed in various cell types, playing crucial roles both physiological and pathological processes, including immune regulation tumorigenesis. Recently, the role of tumors has attracted considerable attention. However, previous pan-cancer studies have reported inconsistencies regarding effects on tumors, particularly concerning its expression levels tumor tissues influence phenotypes cancer cells. This variability believed to stem from context-dependent nature CXCL14, as different sources secretion within distinct microenvironments may mediate diverse biological effects. Such phenomena also been observed prostate research. Despite foundational understanding cancer, there remains lack comprehensive reviews summarizing specific this systematically analyzing reasons behind complex Therefore, article aims discuss microenvironment explore future research directions potential applications.

Language: Английский

Citations

1
Tracing the Evolution of Sex Hormones and Receptor‐Mediated Immune Microenvironmental Differences in Prostate and Bladder Cancers: From Embryonic Development to Disease DOI Creative Commons
Dengxiong Li, Zhipeng Wang, Qingxin Yu

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Abstract The bladder and prostate originate from the urogenital sinus. However, cancer (BC) is usually classified as an immune “hot” tumor, whereas (PCa) deemed “cold” tumor according to microenvironment (TME) clinical outcomes. To investigate differences between BC PCa, studies are compared focusing on regulation mediated by sex hormones receptors identify key genes pathways responsible for differences. From a developmental perspective, it shown that PCa activate similar those in stage. During development, differential expression function of androgen receptor (AR) across cell types may contribute its dual role promoting inhibiting immunity different cells. Androgen deprivation therapy affects AR cells within TME, influencing infiltration antitumor function. Additionally, estrogenα estrogenβ exert contrasting effects BC, which hold potential modifying phenotypes. Future research should target involved development clarify regulatory similarities PCa.

Language: Английский

Citations

1
Cancer-associated fibroblasts and prostate cancer stem cells: crosstalk mechanisms and implications for disease progression DOI Creative Commons
Haoran Chen,

Su-Ping Fang,

Xudong Zhu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2024, Volume and Issue: 12

Published: July 18, 2024

Graphical Abstract Created using Biorender.com .

Language: Английский

Citations

7
Advances in and prospects of immunotherapy for prostate cancer DOI Creative Commons
Deng Liu, Luofu Wang, Yanli Guo

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 601, P. 217155 - 217155

Published: Aug. 8, 2024

Immunotherapy has shown promising therapeutic effects in hematological malignancies and certain solid tumors emerged as a critical highly potential treatment modality for cancer. However, prostate cancer falls under the category of immune-resistant cold tumors, which immunotherapy exhibits limited efficacy patients with tumors. Thus, it is important to gain deeper understanding tumor microenvironment facilitate immune system activation overcome suppression advance In this review, we discuss immunosuppressive cancer, characterized by presence few tumor-infiltrating lymphocytes, abundant cells, low immunogenicity, noninflammatory phenotype, significantly influences mainly achieved activating host overcoming immunosuppression. regard, summarize advances checkpoint blockade, immunogenic cell death, reversal microenvironment, vaccines, adjuvants, chimeric antigen receptor T-cell therapy, penetration barriers aim providing novel research insights approaches enhance effectiveness

Language: Английский

Citations

6
Single cell and spatial transcriptomics highlight the interaction of club-like cells with immunosuppressive myeloid cells in prostate cancer DOI Creative Commons
Antti Kiviaho, Sini K. Eerola, Heini Kallio

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Nov. 16, 2024

Abstract Prostate cancer treatment resistance is a significant challenge facing the field. Genomic and transcriptomic profiling have partially elucidated mechanisms through which cells escape treatment, but their relation toward tumor microenvironment (TME) remains elusive. Here we present comprehensive landscape of prostate TME at multiple points in standard timeline employing single-cell RNA-sequencing spatial transcriptomics data from 120 patients. We identify club-like as key epithelial cell subtype that acts an interface between immune system. Tissue areas enriched with depleted androgen signaling upregulated expression luminal progenitor markers. Club-like display senescence-associated secretory phenotype presence linked to increased polymorphonuclear myeloid-derived suppressor (PMN-MDSC) activity. Our results indicate are associated myeloid inflammation previously deprivation therapy resistance, providing rationale for therapeutic targeting.

Language: Английский

Citations

5
Contemporary Update on Clinical and Experimental Prostate Cancer Biomarkers: A Multi-Omics-Focused Approach to Detection and Risk Stratification DOI Creative Commons

Sana Hachem,

Amani Yehya, Jad El Masri

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(10), P. 762 - 762

Published: Sept. 25, 2024

Prostate cancer remains a significant health challenge, being the most prevalent non-cutaneous in men worldwide. This review discusses critical advancements biomarker discovery using single-omics and multi-omics approaches. Multi-omics, integrating genomic, transcriptomic, proteomic, metabolomic, epigenomic data, offers comprehensive understanding of molecular heterogeneity prostate cancer, leading to identification novel biomarkers therapeutic targets. holistic approach not only enhances specificity sensitivity detection but also supports development personalized treatment strategies. Key studies highlighted include genes, genetic mutations, peptides, metabolites, potential through analyses, which have shown promise improving management. The integration clinical practice can potentially revolutionize prognosis treatment, paving way for precision medicine. underscores importance continued research application overcome current challenges diagnosis therapy.

Language: Английский

Citations

4