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immune checkpoint blockade, 副作用, B16-F10 melanoma tumours, PI3K𝛄, 副作用,…

- - - - 應用
      - 突變量高(melanoma)
        
        大量變異蛋白
        
        T cell 不易察覺
      - 突變量低
        
        不易活化免疫反應
  - - - T cell 正常運作→殺cancer cell
  - - - anti CTLA-4 拮抗（blocker）
        
        T cell 正常運作→殺cancer cell
- - - - anti PD-L1 拮抗(blocker)
        
        T cell 正常運作→殺cancer cell
- - - - infiltrated by suppressive TAMCs
      - lose sensitivity to ICB
      - GMCSF:help shape Me, promote 骨髓生成etc.
- - - - results
      - PI3Kr inhibition affects myeloid cells (X tumor cells or TILs)
      - significant reduction in lung metastasis after IPI-549 treatment.
      - TILs quantification show no consistent differences in total myeloid cells(CD11b+) or macrophages(CD11b+F4/80+)
        →also in IPI-549 or vehicle-treated 4TI or B16-GMCSF
      - switch the activation of macrophages immunosuppressive → more inflammatory state:
        M2-like(CD11b+F4/80+CD206+)→M1-like(CD11b+F4/80+MHCII+)
      - RNA expression: M2 markers↓(TGB𝛃,Arg-1,IDO), M1markers↑(IL-12,INOS)