Immunology · Transplant, tumors and immunotherapy
Cancer immunotherapy: checkpoint inhibitors, CAR-T and vaccines !
- Topic
Some cancer treatments do not attack the tumour directly: they release the brakes of the immune system or train the patient's own T cells to find the cancer.
Updated 2026-11-01
What it is
Cancer immunotherapy uses the immune system to recognise and destroy tumour cells. The main tools are immune checkpoint inhibitors (antibodies that release the PD-1, PD-L1, CTLA-4 or LAG-3 brakes on T cells), adoptive cell therapy (CAR-T cells, tumour-infiltrating lymphocytes), therapeutic monoclonal and bispecific antibodies, treatment vaccines and broad immune modulators. Because they unleash immunity, their typical side effects are autoimmune-like inflammation and, for CAR-T, cytokine release syndrome.
Key facts
- CTLA-4 acts early, limiting T-cell priming in lymph nodes; PD-1 acts late, in tissues, where it marks exhausted T cells.
- Tumours with many mutations (melanoma, smoking-related lung cancer, MSI-high tumours) display more neoantigens and respond better to checkpoint inhibitors.
- A CAR joins an antibody fragment (scFv) that binds a surface antigen to CD3ζ and a costimulatory domain (CD28 or 4-1BB): it recognises antigen without MHC.
- CAR-T cells are made from the patient's own T cells, modified in a laboratory with a viral vector, expanded and infused back; production takes several weeks.
- Current CAR-T targets: CD19 (B-cell acute lymphoblastic leukaemia, large B-cell lymphoma) and BCMA (multiple myeloma).
- Other approaches: tumour-infiltrating lymphocytes, bispecific T-cell engagers (for example CD19 × CD3), intravesical BCG for bladder cancer and preventive vaccines (HPV, hepatitis B) that prevent virus-driven cancers.
Checkpoint inhibitors by class
| Class | What it blocks | Examples | Notes |
|---|---|---|---|
| Anti-PD-1 | PD-1 on exhausted T cells inside the tumour | Nivolumab, pembrolizumab | Melanoma, lung cancer, kidney cancer, Hodgkin lymphoma, tumours with mismatch repair deficiency (MSI-high), among others |
| Anti-PD-L1 | PD-L1 made by tumour and stromal cells | Atezolizumab, durvalumab | Lung and bladder cancer, among others; PD-L1 staining can help select patients |
| Anti-CTLA-4 | CTLA-4, which competes with CD28 for B7 during priming in lymph nodes | Ipilimumab | Melanoma; often combined with anti-PD-1, with more side effects |
| Anti-LAG-3 | LAG-3, another inhibitory receptor on T cells | Relatlimab | Combined with nivolumab in advanced melanoma |
Markers
- PD-1
- PD-L1
- CTLA-4
- LAG-3
- CD19
- BCMA
- MSI-high
- IL-6
Clinical notes
- Immune-related adverse events of checkpoint inhibitors: dermatitis, colitis, hepatitis, pneumonitis, thyroiditis, hypophysitis, type 1 diabetes, nephritis and, rarely, myocarditis.
- CAR-T: cytokine release syndrome (fever, low blood pressure, driven by IL-6; treated with the IL-6 receptor blocker tocilizumab and corticosteroids) and neurotoxicity (ICANS: confusion, speech problems).
- Anti-CD19 CAR-T also destroys normal B cells, giving long-lasting B-cell aplasia and low antibody levels.
- Tumours escape immunotherapy by losing the target antigen or MHC class I, or by recruiting regulatory T cells and suppressive myeloid cells.
Test yourself
Think of the answer, then tap the question to see it.
What is the difference between where CTLA-4 and PD-1 act?
CTLA-4 limits T-cell priming in lymph nodes by competing with CD28 for B7; PD-1 inhibits already activated T cells in peripheral tissues and tumours.
Why can CAR-T cells recognise tumour cells that have lost MHC class I?
The CAR uses an antibody fragment that binds a surface antigen directly, without MHC presentation.
Which cytokine drives cytokine release syndrome after CAR-T therapy, and what drug blocks its receptor?
IL-6; tocilizumab blocks the IL-6 receptor.
A patient on a checkpoint inhibitor develops diarrhoea and fatigue with low cortisol. Which adverse events should be considered?
Immune-related colitis and hypophysitis (or adrenal involvement), autoimmune-like effects of releasing T-cell brakes.
Which antigen is targeted by CAR-T cells in multiple myeloma?
BCMA (B-cell maturation antigen).
Related
- Tumor immunology and checkpoint inhibitors
- Monoclonal antibodies and biologics: naming and targets
- T-cell activation: two signals and superantigens
- CD8⁺ cytotoxic T cell
- Interleukin-6
- Immune tolerance and how autoimmunity begins
- Regulatory T cell (Treg, FOXP3)
Related conditions
In Pharmacology
Educational content on the immune system; not a treatment or individual vaccination guide and no substitute for a health professional's advice. No doses are given.
Sources: Immunotherapy to Treat Cancer (National Cancer Institute (NCI), 2026); Immune Checkpoint Inhibitors (National Cancer Institute (NCI), 2026); CAR T Cells: Engineering Patients’ Immune Cells to Treat Their Cancers (National Cancer Institute (NCI), 2026); Tocilizumab Injection: MedlinePlus Drug Information (U.S. National Library of Medicine (MedlinePlus), 2026).
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Representative model, for educational purposes only.