Macrophage-coated tumor cluster aggravates hepatoma invasion and immunotherapy resistance via generating local immune deprivation.
Cell Rep Med
; 5(5): 101505, 2024 May 21.
Article
en En
| MEDLINE
| ID: mdl-38614095
ABSTRACT
Immune checkpoint inhibitors (ICIs) represent a promising treatment for hepatocellular carcinoma (HCC) due to their capacity for abundant lymphocyte infiltration. However, some patients with HCC respond poorly to ICI therapy due to the presence of various immunosuppressive factors in the tumor microenvironment. Our research reveals that a macrophage-coated tumor cluster (MCTC) signifies a unique spatial structural organization in HCC correlating with diminished recurrence-free survival and overall survival in a total of 572 HCC cases from 3 internal cohorts and 2 independent external validation cohorts. Mechanistically, tumor-derived macrophage-associated lectin Mac-2 binding protein (M2BP) induces MCTC formation and traps immunocompetent cells at the edge of MCTCs to induce intratumoral cytotoxic T cell exclusion and local immune deprivation. Blocking M2BP with a Mac-2 antagonist might provide an effective approach to prevent MCTC formation, enhance T cell infiltration, and thereby improve the efficacy of ICI therapy in HCC.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Carcinoma Hepatocelular
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Microambiente Tumoral
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Inmunoterapia
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Neoplasias Hepáticas
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Macrófagos
Límite:
Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cell Rep Med
Año:
2024
Tipo del documento:
Article