Cellular Dynamics Upon Immune Checkpoint Inhibition

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

Published: July 2, 2024

Abstract Cellular dynamics in the tumor microenvironment upon immune checkpoint inhibition (ICIs) treatment remain largely known. To elucidate these and associated mechanisms of response resistance, we analyzed a large-scale single-cell RNA-sequencing dataset 326 samples from 163 patients across multiple cancer types, with longitudinally site-matched samples. We developed robust, integration-free deep phenotyping framework, annotated 1,022,526 cells into 83 granular cell states. Our analysis revealed consistent compositional changes 19 subtypes during ICI treatment, including enhanced adaptive responses (e.g., CD8+ IL7R+ central memory T cells, GZMK+ effector germinal center B cells), reduced interferon-responsive quiescent CD4+CREM- angiogenesis tip cells. Co-regulatory network continuum between two patterns resembling tertiary lymphoid structure maturity. Accumulation was expansion. further identified cell- centric response-specific pattern indicating an early-phase favored efficacy, which subsequently validated through supervised subgroup analysis. study presents comprehensive landscape TME cellular showcasing importance systems-level understanding improving patient stratification advancing personalized immunotherapy.

Language: Английский

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Single-cell transcriptomics reveals the landscape of esophageal squamous cell carcinoma after neoadjuvant chemoradiotherapy and the potential resistance role of LGALS1

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 25, 2024

Background Neoadjuvant chemoradiotherapy (neoCRT) remodels the tumor microenvironment in esophageal squamous cell carcinoma (ESCC). This study aimed to analyze impact of neoCRT on immune landscape ESCC and identify potential resistance genes using single-cell RNA-seq (scRNA-seq). Methods We obtained scRNA-seq datasets from GEO database evaluated changes number function key T cells myeloid following neoCRT. Malignant epithelial were analyzed inferCNV subjected differential analysis drug-resistance genes. The gene LGALS1, implicated drug resistance, was further investigated. effects short hairpin RNA knockdown LGALS1 cisplatin sensitivity assessed both vitro vivo. Additionally, pathways explored through a protein-protein interaction network set enrichment analysis. Results NeoCRT treatment resulted activation within microenvironment, enhancing anti-tumor response improving eradication compared surgery group. However, simultaneously increased expression cells, which contributed development resistance. Mechanistically, overexpression associated with platinum enhanced DNA repair, apoptosis epithelial-mesenchymal transition. Conclusion revealed that significantly alters ESCC. While activates target effectively, it also induces overexpression, contributes relapse.

Language: Английский

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Intratumoural CD8+ CXCR5+ follicular cytotoxic T cells have prognostic value and are associated with CD19+ CD38+ B cells and tertiary lymphoid structures in colorectal cancer

Cancer Immunology Immunotherapy, Journal Year: 2024, Volume and Issue: 74(1)

Published: Dec. 30, 2024

Colorectal cancer (CRC) is the most common digestive in world. Microsatellite stability (MSS) and microsatellite instability (MSI-high) are important molecular subtypes of CRC closely related to tumor occurrence progression immunotherapy efficacy. The presence CD8

Language: Английский

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