Project description:CD8+ T cell-mediated immune response plays a pivotal role in controlling tumor growth.However, within the tumor microenvironment (TME), prolonged antigen exposure, as well as immunosuppressive factors, drive infiltrated tumor-specific CD8+ T cells into a hyporesponsive state known as “exhaustion”. These Tex cells are mainly characterized by the sustained and elevated expression of a series of inhibitory receptors as well as the hierarchical loss of effector functions. Further, the impaired proliferative capacity of exhausted CD8+ T cells results in decreasing numbers of tumor-specific T cells, such that the residual CD8+ T cells within the TME can barely provide sufficient protective immunity against tumor progression. Thus, the maintenance or reinforcement of intratumoral antigen-specific CD8+ T cells is indispensable for tumor repression. Here, we profiled the transcriptional signatures of antigen-specific CD8+ T cells from tumor draining LN, TIL and PBMC of melanoma bearing mice at single-cell level, aiming to draw a comprehensive immune-atlas of tumor-specific CD8 T cells during tumorigenesis.

2022-10-10 | GSE180094 | GEO

A chemokine trail laid down by migratory dendritic cells directs antigen-presenting monocytes into draining lymph nodes

Project description:Antigen presenting dendritic cells (DCs) and monocytes capture and transport antigens from barrier tissues for presentation to antigen-specific T cells in the draining-lymph nodes (LNs). While DCs enter LNs through afferent lymphatics in a CCR7-dependent manner, how exactly antigen-carrying monocytes reach LNs is less clear since monocytes do not express CCR7 and can also enter LNs via the bloodstream. In steady state, and following injection of several PAMPs, scRNA-seq data on LN mononuclear phagocytes identified LN resident versus migratory type 1 and type 2 conventional (c)DCs despite downregulation of DC subset-defining transcripts, such as Xcr1, Clec9a, H2-Ab1, Sirpa, and Clec10a on migratory cDCs. Migratory cDCs gained expression of transcripts controlling cellular migration such as Ccr7, Ccl17, Ccl22, and Ccl5, while migratory monocytes expressed Ccr5 without Ccr7. Using two tracking methods and a gating strategy that clearly distinguishes migratory CD88hiCD26lo monocytes from CD88-CD26hi cDCs, we found that both captured antigens in the lung and migrated to lung-draining LNs. Using global and mixed-chimeric Ccl5-, Ccr2-, Ccr5-, Ccr7-, and Batf3-deficient mice, we found that CCR5+ monocytes follow CCL5-secreting migratory cDCs to reach the draining LN via lymphatic vessels. In a model of asthma, such recruited monocytes regulated the induction of type 2 immunity. Overall, our data suggest that CCL5-secreting migratory cDCs lay down the chemokine trail for CCR5+ antigen-presenting monocytes to reach draining lymph nodes and regulate adaptive immunity.

2022-10-17 | GSE215299 | GEO

Next Generation Sequencing Quantitative Analysis of altered expression of genes in bladder cancer derived EVs educated draining LNs

Project description:Metastasis of tumors to LNs predicts disease progression and poor outcomes of patients. Recent studies revealed that tumor cells deliver EVs to particular targeted recipient cells in draining LNs and subsequently alter their gene expression patterns to create a supportive pre-metastatic niche to promote LN metastasis. Yet, the biological role and underlying mechanism of bladder cancer derived EVs (BCa derived EVs) in mediating lymphatic pre-metastatic niche formation remain unclear. The present study aim to explore the differential genes of BCa derived EVs educated draining LNs and underlying mechanism in the lymphatic pre-metastatic niche formation.

2024-10-10 | GSE246070 | GEO

scRNA-seq of antigen-specific CD8+ T cells from tumor draining LN, TIL and PBMC of melanoma bearing mice

Project description:scRNA-seq of antigen-specific CD8+ T cells from tumor draining LN, TIL and PBMC of melanoma bearing mice

| PRJNA746548 | ENA

Immune response genes at the mRNA vaccine delivery sites and draining lymph nodes of rhesus macaques

Project description:mRNA vaccines are emerging as a powerful vaccine platform as they are well-tolerated and scalable. Modified non-replicating mRNA encoding Influenza hemagglutinin and encapsulated in lipid nanoparticles (LNP) induced robust antibody and CD4 T cell responses after intramuscular or intradermal delivery in rhesus macaques. We investigated the local innate immune responses modulating such vaccine-induced immunity at the sites of immunization (skeletal muscle and skin) and their draining lymph nodes (LNs). Rapid mobilization of antigen presenting cells was found at the LNP/mRNA-injection sites and LNs. Dendritic cells efficiently internalized the LNPs, translated the mRNA cargo and upregulated co-stimulatory molecules. In addition, several type I interferon-inducible genes were expressed at the immunization sites and draining LNs. The innate immune activation was transient and resulted in priming of antigen-specific CD4+ T cells exclusively in the vaccine-draining LNs. Collectively, mRNA-based vaccines induce type I interferon-polarized innate immunity and antigen production by antigen presenting cells, which resulted potent vaccine-specific responses.

2017-04-26 | GSE98211 | GEO

Analysis of classical and migratory DC from the skin draining LNs of Flt3L treated mice and comparison to LPS treated DC from skin draining LN and peritoneal macrophages

Project description:Analysis of the differential transcriptome of DC derived from tissue vs. LN origin. The overall hypothesis is these data would reveal how migratory DC may be differently programmed from classical DC and might also suggest difference within migratory DC subsets relating to function. RNA obtained from migratory DC subsets and classical CD8a DC isolated by flow cytometry sorting from skin draining LNs of Flt3L treated mice or LPS treated mice

2014-08-01 | E-GEOD-53588 | biostudies-arrayexpress

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