How tumours evade the immune system !
- Mechanism
The immune system can recognise and kill cancer cells. Tumours that survive learn to hide from T cells and to switch them off.
Updated 2026-11-01
What it is
Cytotoxic T cells recognise tumour antigens (neoantigens from mutated proteins, viral proteins, overexpressed self proteins) and kill tumour cells; NK cells kill cells that lose MHC class I. Through immunoediting, the clones that survive are those that hide (loss of MHC class I or antigen) or actively suppress immunity (PD-L1, regulatory T cells, suppressive cytokines). Blocking these brakes with checkpoint inhibitors is now standard therapy for many cancers.
Step by step
- Tumour cells express abnormal antigens presented on MHC class I.
- Dendritic cells cross-present these antigens and prime CD8 T cells in lymph nodes.
- Primed T cells reach the tumour and kill antigen-bearing cells; NK cells kill cells lacking MHC class I.
- Selection favours clones that lose MHC class I, antigen-processing proteins or the target antigen.
- Tumour cells and the microenvironment express PD-L1 and recruit regulatory T cells and suppressive myeloid cells.
- Exhausted T cells stop killing; the tumour escapes and grows.
Tumour escape strategies
| Strategy | Mechanism | Clinical counterpart |
|---|---|---|
| Hide the antigen | Loss of MHC class I, beta-2 microglobulin or antigen | Resistance to checkpoint inhibitors |
| Switch off T cells | PD-L1 binds PD-1 | Anti-PD-1 and anti-PD-L1 antibodies |
| Block priming | CTLA-4 competes for B7 on antigen-presenting cells | Anti-CTLA-4 antibodies |
| Suppressive environment | Regulatory T cells, TGF-beta, IL-10, suppressive macrophages | Poor T-cell infiltration (cold tumours) |
| Exploit a weak host | HIV or transplant immunosuppression | Kaposi sarcoma, EBV lymphomas, HPV-related cancers |
Clinical notes
- Checkpoint inhibitors are used in melanoma, lung, kidney and many other cancers, and in any mismatch repair-deficient tumour.
- Their side effects are immune-related: colitis, hepatitis, pneumonitis, thyroiditis, hypophysitis, dermatitis.
- Merkel cell carcinoma, often driven by a polyomavirus, is very immunogenic and responds to PD-1 or PD-L1 blockade.
Test yourself
Think of the answer, then tap the question to see it.
Why do NK cells matter when tumours lose MHC class I?
NK cells kill cells lacking MHC class I (missing self), which partly offsets this escape strategy.
What is the role of PD-L1 on tumour cells?
It binds PD-1 on activated T cells and inhibits them, causing T-cell exhaustion.
Why does Hodgkin lymphoma respond well to PD-1 blockade?
Reed-Sternberg cells often amplify 9p24.1, which carries the PD-L1 and PD-L2 genes, so the tumour depends on this brake.
Why do mismatch repair-deficient tumours respond to checkpoint inhibitors?
They carry many mutations, producing many neoantigens that T cells can recognise once released from inhibition.
Related
- The hallmarks of cancer
- Genomic instability: mismatch repair, BRCA and xeroderma pigmentosum
- Oncogenic viruses and H. pylori: the table to know
- Invasion and metastasis: the metastatic cascade, step by step
Related conditions
- Melanoma
- Hodgkin lymphoma
- Lung cancer
- Lynch syndrome (hereditary non-polyposis colorectal cancer)
- Colorectal cancer
- Renal cell carcinoma
- Kaposi sarcoma
- HIV infection and AIDS
- Merkel cell carcinoma
- Cervical cancer
Elsewhere in DurgiPedia
- Tumor immunology and checkpoint inhibitors
- Cancer immunotherapy: checkpoint inhibitors, CAR-T and vaccines
- Natural killer cell
- CD8⁺ cytotoxic T cell
- Regulatory T cell (Treg, FOXP3)
- MHC/HLA class I and II
- Secondary immunodeficiency: HIV, malnutrition, drugs, asplenia
Microorganisms
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Immune Checkpoint Inhibitors (National Cancer Institute (NCI), 2026); Targeted Therapy to Treat Cancer (National Cancer Institute (NCI), 2026); What Is Cancer? (National Cancer Institute (NCI), 2026).
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Representative model, for educational purposes only.