Single-cell mass cytometric analysis of peripheral immunity and multiplex plasma marker profiling of non-small cell lung cancer patients receiving PD-1 targeting immune checkpoint inhibitors in comparison with platinum-based chemotherapy

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 13, 2023

The effect of platinum-based chemotherapy (Chem.) and second- or multiple- line immune checkpoint PD-1 blocking therapy by Nivolumab Pembrolizumab (ICI) was assayed in the peripheral blood non-small cell lung cancer (NSCLC) patients.Flow cytometry used to detect NSCLC-related antigen binding IgG antibodies. Luminex MagPix multiplex bead-based cytokine/chemokine detecting system quantitatively measure 17 soluble markers plasma samples. Single-cell mass applied for immunophenotyping leukocytes.The incubation patient derived with human NSCLC tumor lines, such as A549, H1975, H1650, detected NSCLC-specific antibodies reaching a maximum up 32% reactive IgG-positive cells. following were significantly higher concentration Chem. group versus healthy non-smoker smoker controls: BTLA, CD27, CD28, CD40, CD80, CD86, GITRL, ICOS, LAG-3, PD-1, PD-L1, TLR-2. ICI We showed induction CD69 IL-2R on CD4+ CD25+ T-cells upon chemotherapy; exhaustion one CD8+ T-cell population loss CD127 decrease CD27. CD19+CD20+, CD79B+, activated B-cell subtypes increase downregulation patients ICI.Peripheral immunophenotype caused shown context advanced NSCLC.

Language: Английский

---

Reliable Identification and Interpretation of Single‐Cell Molecular Heterogeneity and Transcriptional Regulation using Dynamic Ensemble Pruning

Advanced Science, Journal Year: 2023, Volume and Issue: 10(22)

Published: June 8, 2023

Abstract Unsupervised clustering is an essential step in identifying cell types from single‐cell RNA sequencing (scRNA‐seq) data. However, a common issue with unsupervised models that the optimization direction of objective function and final generated labels absence supervised information may be inconsistent or even arbitrary. To address this challenge, dynamic ensemble pruning framework (DEPF) proposed to identify interpret molecular heterogeneity. In particular, silhouette coefficient‐based indicator developed determine bi‐objective function. addition, hierarchical autoencoder employed project high‐dimensional data onto multiple low‐dimensional latent space sets, then produced by basic algorithm. Following that, fruit fly algorithm designed prune dynamically low‐quality ensemble. Multiple experiments are conducted on 28 real scRNA‐seq datasets one large dataset diverse platforms species validate effectiveness DEPF. biological interpretability transcriptional post‐transcriptional regulatory explore patterns identified, which could provide novel insights into characterizing mechanisms.

Language: Английский

---

The Evolving Landscape of B Cells in Cancer Metastasis

Cancer Research, Journal Year: 2023, Volume and Issue: 83(23), P. 3835 - 3845

Published: Oct. 10, 2023

Metastasis is the leading cause of cancer mortality. Functional and clinical studies have documented diverse B-cell antibody responses in metastasis. The presence B cells tumor microenvironments metastatic sites has been associated with effects that can promote or inhibit Specifically, contribute to spread by enhancing cell motility, invasion, angiogenesis, lymphangiogenesis, extracellular matrix remodeling. Moreover, they colonization triggering pathogenic immunoglobulin recruiting immune suppressive cells. Contrastingly, also exhibit antimetastatic effects. For example, aid enhanced antigen presentation, which helps activate against In addition, play a crucial role preventing dissemination from primary secrete antibodies recognition. Here, we review complex roles metastasis, delineating heterogeneity activity subtypes site, class, (if known), molecular phenotype. These important attributes emphasize need for deeper understanding characterization phenotypes define their

Language: Английский

---

Cell competition promotes metastatic intestinal cancer through a multistage process

iScience, Journal Year: 2024, Volume and Issue: 27(5), P. 109718 - 109718

Published: April 11, 2024

Cell competition plays an instrumental role in quality control during tissue development and homeostasis. Nevertheless, cancer cells can exploit this process for their own proliferative advantage. In our study, we generated mixed murine organoids microtissues to explore the impact of cell on liver metastasis. Unlike at primary site, initial effect progenitor does not involve induction apoptosis. Instead, metastatic manifests as a multistage process. Initially, progenitors undergo compaction, which is followed by cell-cycle arrest, ultimately forcing differentiation. Subsequently, newly differentiated exhibit reduced cellular fitness, rendering them more susceptible outcompetition intestinal cells. Notably, leverage different interactions with epithelial populations liver, using scaffolds facilitate growth. Consequently, tissue-specific mechanisms are fundamental driving cancer.

Language: Английский

---

Single‐cell analysis revealed a potential role of T‐cell exhaustion in colorectal cancer with liver metastasis

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(8)

Published: April 1, 2024

Abstract Liver metastasis (LM) is an important factor leading to colorectal cancer (CRC) mortality. However, the effect of T‐cell exhaustion on LM in CRC unclear. Single‐cell sequencing data derived from Gene Expression Omnibus database. Data were normalized using Seurat package and subsequently clustered annotated into different cell clusters. The differentiation trajectories epithelial cells T characterized based pseudo‐time analysis. Single‐sample gene set enrichment analysis (ssGSEA) was used calculate scores for clusters identify enriched biological pathways. Finally, communication performed. Nine subpopulations identified samples with LM. proportion increased can be subdivided NK/T cells, regulatory (Treg) exhausted (Tex). In LM, adhesion proliferation activity Tex promoted. Epithelial categorized six subpopulations. transformation primary involved two evolutionary branches cells. at beginning trajectory but end receptor ligands CEACAM5 ADGRE5‐CD55 played critical roles interactions between Treg cell‐epithelial cell, which may promote epithelial‐mesenchymal transition process CRC. are able CRC, turn promotes tumour development. This provides a new perspective treatment diagnosis

Language: Английский

---