癌细胞不只是在随机生长——它们正在主动学习如何致盲免疫系统
Level 3 | Core Theory: The Six Immune Evasion Strategies of Cancer Cells
| Strategy | Mechanism |
|---|---|
| Downregulating MHC-I to Evade T Cells | Reducing or eliminating MHC-I molecules on the cell surface, rendering CD8+ T cells unable to recognize tumor antigens. |
| Expressing PD-L1 to Shut Down T Cells | Expressing PD-L1 on the cell surface to bind with PD-1 on T cells, directly shutting down approaching T cells. |
| Losing Tumor Antigens to Eliminate Targets | Mutating to lose or silence genes that produce tumor antigens, leaving the immune system with no target to recognize. |
| Secreting Immunosuppressive Factors | Secreting immunosuppressive cytokines like TGF-β and IL-10 to create a localized microenvironment that suppresses immune activity. |
| Recruiting Immunosuppressive Cells | Attracting Treg cells and MDSCs (Myeloid-Derived Suppressor Cells) into the tumor to suppress immune attacks from within. |
| Inactivating NK Cells ("Anergy") | Secreting TGF-β to inhibit NK cell activity, or upregulating non-classical MHC-I molecules like HLA-E to bind with inhibitory receptors on NK cells. |
Diagram: Immune Evasion Strategies and Therapeutic Intervention Targets
PD-L1 shuts down T cells → Anti-PD-1 (Nivolumab, Pembrolizumab) / Anti-PD-L1 (Atezolizumab) to lift the blockade.
CTLA-4 inhibits T cell activation → Anti-CTLA-4 (Ipilimumab) to block this brake.
MHC-I downregulation evades T cells → NK cell therapy (bypasses this evasion pathway as it does not rely on MHC-I recognition).
HLA-E inhibits NK cells → Anti-NKG2A monoclonal antibody (Monalizumab, under development) to release the blockade on NK cells.
TGF-β systemic immunosuppression → TGF-β pathway inhibitors (multiple under development), combined with checkpoint inhibitors for a synergistic effect.
M2 macrophage subversion → CSF-1R inhibitors / macrophage polarization intervention, turning accomplices back into enemies.
