Macrophage Immunosuppressive Phenotype [Neurosurgery Wiki]

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====== Macrophage Immunosuppressive Phenotype ======

The '''immunosuppressive phenotype''' of macrophages refers to a functional state in which macrophages suppress immune responses rather than promote them. This phenotype is particularly relevant in [[tumor microenvironment|tumors]], [[chronic inflammation]], and [[neurodegeneration]].

===== Characteristics =====

Macrophages with an immunosuppressive phenotype exhibit:

  * Secretion of anti-inflammatory cytokines:
    * '''IL-10'''
    * '''TGF-β'''
  * Expression of immune checkpoint molecules:
    * '''PD-L1'''
    * '''CTLA-4'''
  * Metabolic changes that impair T cell activation (e.g., via '''Arginase-1''')
  * Promotion of angiogenesis and extracellular matrix remodeling
  * Suppression of cytotoxic T cell and NK cell activity

===== In Gliomas =====

In gliomas, macrophages are often reprogrammed into an M2-like, immunosuppressive phenotype, contributing to tumor immune evasion.

  * These macrophages are known as '''tumor-associated macrophages (TAMs)'''
  * Glioma-derived factors (e.g., CSF-1, VEGF, lactate) polarize TAMs
  * Recent studies show that:
    * '''ANXA1''' promotes the immunosuppressive phenotype in glioma TAMs
    * Methionine metabolism is involved in epigenetic reprogramming

===== Key Markers =====

^ Marker ^ Role ^
| '''Arginase-1 (Arg1)''' | Depletes L-arginine → T cell suppression |
| '''PD-L1''' | Inhibits T cell activation via PD-1 |
| '''IL-10''' | Suppresses pro-inflammatory cytokines |
| '''TGF-β''' | Immunosuppressive and pro-fibrotic effects |
| '''CD163''', '''CD206''' | Surface markers of M2-like macrophages |

===== Clinical Implications =====

Targeting the immunosuppressive phenotype of macrophages is a key strategy in:

  * [[Cancer immunotherapy]] (e.g., anti-CSF1R therapy)
  * [[Glioblastoma treatment]]
  * [[Neurodegenerative disease modulation]]

Reprogramming TAMs toward a pro-inflammatory, tumoricidal phenotype (M1-like) is under active investigation.