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. 2023 Nov 7;30(11):9789–9812. doi: 10.3390/curroncol30110711

Table 6.

Immunotherapy resistance mechanisms [104,105].

Internal Mechanisms External Mechanisms
  • 1.
    Gene mutation: [41,100]
    • a.
      CTNNB1 mutation: [106]
    • ↑ Wnt/beta-catenin pathway associated with ↑ T reg cells, ↓ CD8+ T cells
  • 1.
    ↑ Immune checkpoints: [105]
    • a.
      PD-1
    • b.
      PD-L1
    • c.
      CTLA-4
    • d.
      LAG-3
    • e.
      TIM-3
    • f.
      TIGIT
  • 2.
    Gene expression variation: [107]
    • a.
      ↓ CD274 gene expression (PD-L1 mRNA) associated with ↓ benefit from atezolizumab + bevacizumab
  • 2.
    ↓ CD8+ T cells: [108]
    • a.
      ↑ Pro-tumor state
  • 3.

    ↓ Tumor mutational burden *: [105]
  • 3.
    ↑ T reg cells: [108]
    • a.
      ↑ Pro-tumor state

* Association of high TMB and ICI resistance has inconsistent data in the literature for HCC.