The tumor microenvironment (TME) has a significant impact on tumor growth and immunotherapy efficacies. However, the precise cellular interactions and spatial organizations within the TME that drive these effects remain elusive. Using advanced multiplex imaging techniques, we have discovered that regulatory T cells (Tregs) accumulate around lymphatic vessels in the peripheral tumor stroma. This localized accumulation is facilitated by mature dendritic cells enriched in immunoregulatory molecules (mregDCs), which promote chemotaxis of Tregs, establishing a peri-lymphatic Treg-mregDC niche. Within this niche, mregDCs facilitate Treg activation, which in turn restrains the trafficking of tumor antigens to the draining mesenteric lymph nodes, thereby impeding the initiation of anti-tumor adaptive immune responses. Disrupting Treg recruitment to mregDCs inhibits tumor progression. Our study provides valuable insights into the organization of TME and how local crosstalk between lymphoid and myeloid cells suppresses anti-tumor immune responses.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ccell.2024.06.014 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Predicting microRNAs and their Target Genes Involved in Sepsis Pathogenesis by using Bioinformatics Methods.
Curr Pharm Des
January 2025
Healthy Ageing Research Center, Neyshabur University of Medical Sciences, Neyshabur, Iran.
Introduction: Sepsis, like neutropenic sepsis, is a medical condition in which our body overreacts to infectious agents. It is associated with damage to normal tissues and organs by the immune system, which leads to the spread of inflammation throughout our body. Of note, microRNAs (miRNAs) have been found to have a critical role in the sepsis progression.
View Article and Find Full Text PDFA Novel Protein NLRP12-119aa that Prevents Rhabdovirus Replication by Disrupting the RNP Complex Formation.
Adv Sci (Weinh)
January 2025
Laboratory of Fish Molecular Immunology, College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, 201306, China.
The accurate assembly of the ribonucleoprotein (RNP) complex is fundamental for the replication and transcription of rhabdoviruses, which are known for their broad pathogenic impact. A novel 119-amino-acid protein, NLRP12-119aa is identified, encoded by the circular RNA circNLRP12, that effectively disrupts the formation of rhabdovirus RNP complexes through two distinct mechanisms and significantly reduces their replication. NLRP12-119aa exhibits a strong affinity for the conserved 18-nucleotide sequence at the start of the leader RNA of rhabdoviruses VSV, SCRV, and RABV, outcompeting their native N protein interactions, thereby disrupting the assembly of RNP complexes and inhibiting viral replication.
View Article and Find Full Text PDFMicroenvironmental β-TrCP negates amino acid transport to trigger CD8 T cell exhaustion in human non-small cell lung cancer.
Cell Rep
January 2025
The Fourth Affiliated Hospital of Soochow University, Institutes of Biology and Medical Sciences, Suzhou Medical College of Soochow University, Soochow University, Suzhou, China; Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China. Electronic address:
CD8 T cell exhaustion (Tex) has been widely acknowledged in human cancer, while the underlying mechanisms remain unclear. Here, we demonstrate that reduced amino acid (aa) metabolism and mTOR inactivation are accountable for Tex in human non-small cell lung cancer (NSCLC). NSCLC cells impede the T cell-intrinsic transcription of SLC7A5 and SLC38A1, disrupting aa transport and consequently leading to mTOR inactivation.
View Article and Find Full Text PDFNonhuman primate antigenic cartography of SARS-CoV-2.
Cell Rep
January 2025
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address:
Virus neutralization profiles against primary infection sera and corresponding antigenic cartography are integral part of the COVID-19 and influenza vaccine strain selection processes. Human single variant exposure sera have previously defined the antigenic relationships among SARS-CoV-2 variants but are now largely unavailable due to widespread population immunity. Therefore, antigenic characterization of future SARS-CoV-2 variants will require an animal model, analogous to using ferrets for influenza virus.
View Article and Find Full Text PDFA prospective, phase II, neoadjuvant study based on chemotherapy sensitivity in HR+/HER2- breast cancer-FINEST study.
Cancer Commun (Lond)
January 2025
Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Centre, Shanghai, P. R. China.
Background: Hormone receptor-positive (HR+)/humaal growth factor receptor 2-negative (HER2-) breast cancer, the most common breast cancer type, has variable prognosis and high recurrence risk. Neoadjuvant therapy is recommended for median-high risk HR+/HER2- patients. This phase II, single-arm, prospective study aimed to explore appropriate neoadjuvant treatment strategies for HR+/HER2- breast cancer patients.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!