Immune Evasion: Mechanisms in Cancer
What is Immune Evasion?
Immune evasion is a set of strategies used by cancer cells to avoid detection and destruction by the body’s immune system. Normally, the immune system recognizes and attacks abnormal or cancerous cells, but tumors can develop ways to escape this immune surveillance, allowing them to grow and spread unchecked.
Major Mechanisms of Immune Evasion
- Reduced Antigen Recognition: Cancer cells decrease the expression of major histocompatibility complex class I (MHC-I) molecules or alter tumor antigens to avoid detection by T cells. This reduces effective immune recognition and activation.
- Inhibition of Immune Cell Infiltration: Tumors alter the microenvironment to prevent immune cells like CD8+ T cells from migrating into tumor tissues, often by modifying chemokine signals and vascular factors.
- Immunosuppressive Tumor Microenvironment (TME): Tumors recruit regulatory immune cells (e.g., Tregs, myeloid-derived suppressor cells) and secrete immunosuppressive cytokines (IL-10, TGF-β), creating a local environment that inhibits effective anti-tumor immune responses.
- Immune Checkpoint Activation: Upregulation of checkpoint molecules such as PD-L1 on tumor cells binds PD-1 on T cells, inhibiting their activity and preventing tumor cell killing.
- Shedding or Modifying NK Cell Ligands: Tumor cells may shed ligands like NKG2D ligands to avoid recognition and killing by natural killer (NK) cells.
Impact on Cancer Treatment
Immune evasion contributes to tumor resistance against immunotherapies like checkpoint inhibitors. Understanding these mechanisms is critical for developing new strategies to overcome immune resistance and improve therapeutic efficacy.
Key Points
- Immune evasion enables tumors to escape immune detection and destruction.
- Mechanisms include antigen downregulation, immune cell exclusion, immunosuppressive microenvironment, immune checkpoint activation, and NK cell evasion.
- These processes limit immune therapy effectiveness and promote tumor progression.
- Research focuses on targeting these pathways to enhance anti-tumor immunity.
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References:
Zhou Z, Chen J, Li H, et al. Immune evasion through mitochondrial transfer in the tumor microenvironment. Nat Rev Cancer. 2025 Jan;24(1):28-42. doi:10.1038/s41568-024-00839-2. Available at: https://www.nature.com/articles/s41586-024-08439-0
