Unlabelled: The tumor microenvironment (TME) represents a complex network in which tumor cells communicate not only with each other but also with stromal and immune cells. The intercellular interactions in the TME contribute to tumor initiation, progression, metastasis, and treatment outcome. Recent advances in spatial transcriptomics (ST) have revolutionized the molecular understanding of the TME at the spatial level. A comprehensive interactive analysis resource specifically designed for characterizing the spatial TME could facilitate further advances using ST. In this study, we collected 296 ST slides covering 19 cancer types and developed a computational pipeline to delineate the spatial structure along the malignant-boundary-nonmalignant axis. The pipeline identified differentially expressed genes and their functional enrichment, deconvoluted the cellular composition of the TME, reconstructed cell type-specific gene expression profiles at the sub-spot level, and performed cell-cell interaction analysis. Finally, the user-friendly database SpatialTME (http://www.spatialtme.yelab.site/) was constructed to provide search, visualization, and downloadable results. These detailed analyses are able to reveal the heterogeneous regulatory network of the spatial microenvironment and elucidate associations between spatial features and tumor development or response to therapy, offering a valuable resource to study the complex TME.
Significance: SpatialTME provides spatial structure, cellular composition, expression, function, and cell-cell interaction information to enable investigations into the tumor microenvironment at the spatial level to advance understanding of cancer development and treatment.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1158/0008-5472.CAN-23-2650 | DOI Listing |
PLoS One
January 2025
Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Triple negative breast cancers often contain higher numbers of tumour-infiltrating lymphocytes compared with other breast cancer subtypes, with their number correlating with prolonged survival. Since little is known about tumour-infiltrating lymphocyte trafficking in triple negative breast cancers, we investigated the relationship between tumour-infiltrating lymphocytes and the vascular compartment to better understand the immune tumour microenvironment in this aggressive cancer type. We aimed to identify mechanisms and signaling pathways responsible for immune cell trafficking in triple negative breast cancers, specifically of basal type, that could potentially be manipulated to change such tumours from immune "cold" to "hot" thereby increasing the likelihood of successful immunotherapy in this challenging patient population.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Yunnan Key Laboratory of Stem Cell and Regenerative Medicine, Kunming Medical University, Kunming, 650500, China.
Small molecules as nanomedicine carriers offer advantages in drug loading and preparation. Selecting effective small molecules for stable nanomedicines is challenging. This study used artificial intelligence (AI) to screen drug combinations for self-assembling nanomedicines, employing physiochemical parameters to predict formation via machine learning.
View Article and Find Full Text PDFSci Adv
January 2025
Department of Allergy, the First Affiliated Hospital of Anhui Medical University and Institute of Clinical Immunology, Anhui Medical University, Hefei 230032, China.
Type 2 innate lymphoid cells (ILC2s) mainly reside in tissues with few lymphoid cells. How their tissue residency is regulated remains poorly understood. This study explores the inhibitory role of SLAM-family receptors (SFRs) on adaptive immune cells in ILC2 maintenance.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
School of Pharmaceutical Sciences, Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Zhengzhou University, Zhengzhou, 450001, China.
Although cytotoxic T lymphocytes (CTLs) activation combined with programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis blockade have emerged as an effective strategy to improve immunotherapeutic potency, it remains challenging to realize the spatiotemporal synergy of these two components. Herein, the study reports an engineered bacterial-based delivery system that can simultaneously promote CTLs infiltration and control PD-L1 binding protein (PD-L1 trap) release on demand at tumor site. The drug release button of this tumor targeting system is the specific temperature, which is accomplished by dual-modified melanin nanoparticles with photothermal conversion capacity on the engineered bacterial.
View Article and Find Full Text PDFOMICS
January 2025
Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, India.
There is a growing interest in harnessing natural compounds and bioactive phytochemicals to accelerate drug discovery and development, including in the treatment of human cancers. Receptor tyrosine kinases (RTKs) are critical regulators of many fundamental cellular processes and have been implicated in cancer pathogenesis as well as targets for anticancer drug development. The members of TAM, Tyro3, Axl, and MERTK subfamily RTKs, especially Mer, affect immune homeostasis in the tumor microenvironment.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!