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Macrophages Coated Tumor Cluster (MCTC) Aggravated Hepatoma Invasion and Immunotherapy Resistance via Entrapping Cytotoxic T Cells to Generate Local Immune Deprivation in a M2BP-dependent manner

GSE248907 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2024/06/12 Platform GPL24676
Summary
Immune checkpoint inhibitors (ICIs) represent promising treatment for hepatocellular carcinoma (HCC) due to abundant lymphocyte infiltration. However, some HCC patients respond poorly to ICI therapy due to the presence of various immunosuppressive factors in tumor microenvironment. Our research revealed that macrophage-coated tumor clusters (MCTCs) signified a unique spatial structural organization in HCC, correlating with diminished recurrence-free survival (RFS) and overall survival (OS) in a total of 572 HCC cases from 3 internal cohorts and 2 external validation cohort independently. Mechanistically, Tumor-derived M2BP induced MCTCs formation, and entrapped immunocompetent cells at the edge of MCTCs to induce intratumoral cytotoxic T cells exclusion and local immune deprivation. Combined treatment of anti-PD-1 antibody and Mac-2 antagonist GB1107 before MCTC formation could significantly attenuated HCC growth and inhibited HCC metastasis in vivo by recovering intratumoral infiltration of cytotoxic T cells, offering a potential strategy to enhance ICI efficacy in HCC.
Published in
Macrophage-coated tumor cluster aggravates hepatoma invasion and immunotherapy resistance via generating local immune deprivation
Ning J, Ye Y, Shen H et al. · Cell reports. Medicine 2024 · PMID 38614095 · doi:10.1016/j.xcrm.2024.101505
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Also filed as BioProject PRJNA1046433 and SRA study SRP474880. Searching any of these in the dataset finder brings you back here.

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