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    How the immune system fights cancer, and how tumours escape

    The immune system can recognise and attack cancer cells, but tumours escape by becoming less visible, by displaying proteins that switch immune cells off, and by changing the tissue around them.[1] Every cancer immunotherapy targets one or more of these escape routes.[2]

    Editor reviewedStrict sourcingUpdated Cancer immunotherapyHealth and medicineLife sciences

    The immune system patrols the body for abnormal cells, and immunotherapy is treatment that helps it fight cancer.[3] To understand why some immunotherapies work and others fail, it helps to know how tumours escape immune attack in the first place.[1]

    Recognition: how T cells see cancer

    T cells are the immune system’s targeted killers. Each one recognises a specific mark, or antigen. Cancer cells carry mutations, and some mutations create new marks called neoantigens that T cells can learn to spot.[4] Some patients’ tumours already contain T cells that recognise the cancer but are too few to clear it.[5]

    Tumour-specific neoantigens arising from somatic mutations are the basis of personalised vaccines, which encode dozens of patient-specific epitopes (up to 34 in intismeran autogene).[4] Tumour-infiltrating lymphocytes show that tumour-reactive T cells often exist in situ, but in insufficient number or function to control disease.[5]

    Escape: how tumours hide

    NCI describes three main escape routes. Cancer cells can change so the immune system sees them less well. They can display proteins that switch immune cells off. And they can change the healthy cells around them so these block the immune response.[1]

    The three escape mechanisms NCI lists map onto reduced immunogenicity, inhibitory ligand expression, and an immunosuppressive tumour microenvironment.[1] The microenvironment and antigen heterogeneity are also the main reasons engineered T cells struggle in solid tumours.[6]

    Brakes: immune checkpoints

    The immune system has built-in brakes called checkpoints. They stop immune attacks from becoming so strong that they harm healthy tissue.[7] Some tumours press these brakes on purpose, for example by making lots of a protein called PD-L1.[8] Drugs that block checkpoints let T cells attack again, but because the brakes also protect healthy organs, side effects can include inflammation.[9]

    CTLA-4 acts mainly during T-cell priming in lymph nodes, whereas PD-1 acts mainly in peripheral tissues, where its ligands PD-L1 and PD-L2 are expressed in the tumour microenvironment.[10] Tumours that overexpress PD-L1 dampen effector T-cell responses, and blocking the PD-1/PD-L1 interaction restores them.[8] Toxicity follows from the same biology: immune-related adverse events occurred in 64% of patients in an ipilimumab melanoma trial.[11]

    Fixes: what each therapy targets

    Each type of immunotherapy fixes a different problem. Checkpoint inhibitors release the brakes.[8] Cell therapies supply more, or better-aimed, T cells.[12] Vaccines teach the immune system what to look for.[13] Bispecific antibodies drag T cells directly to cancer cells.[14]

    Checkpoint blockade reinvigorates existing immunity; adoptive transfer (TIL, CAR-T) bypasses priming by supplying effector cells; vaccines attempt de novo priming against neoantigens; and CD3-based bispecifics redirect T cells to a surface antigen.[8][12][15][14] The modest share of patients who respond to checkpoint inhibitors, estimated at about 12.5% in the US in 2018, motivates combining these approaches.[16]

    Next in the course: how CAR-T cell therapy works, then how cancer vaccines work.

    Questions readers ask

    If the immune system can kill cancer cells, why do cancers grow?

    According to NCI, cancer cells can have genetic changes that make them less visible, carry surface proteins that turn off immune cells, and change the normal cells around the tumour.[1]

    What is an immune checkpoint?

    A normal part of the immune system that stops immune responses from becoming so strong that they destroy healthy cells.[7]

    Why does immunotherapy cause inflammation side effects?

    Releasing immune brakes can lead to inflammation in healthy organs. Rarer checkpoint-inhibitor side effects include widespread inflammation affecting organs such as the lungs, colon, liver and thyroid.[9]

    Sources

    Each numbered claim is a statement we checked against the sources listed with it. Status shows how well established it is.

    1. [1]

      According to NCI, cancer cells can escape the immune system through genetic changes that make them less visible, surface proteins that switch off immune cells, and changes to the normal cells around the tumour. confirmedas of 2026-10-10

    2. [2]

      NCI lists the main types of cancer immunotherapy as immune checkpoint inhibitors, T-cell transfer therapy, monoclonal antibodies, treatment vaccines and immune system modulators. confirmedas of 2026-10-10

    3. [3]

      The US National Cancer Institute defines immunotherapy as a type of cancer treatment that helps the immune system fight cancer. confirmedas of 2026-10-10

    4. [4]

      Intismeran autogene (mRNA-4157/V940), co-developed by Merck and Moderna, is an individualised mRNA therapy encoding up to 34 neoantigens chosen from each patient's tumour. confirmedas of 2026-08-19

    5. [5]

      TIL therapy takes lymphocytes from a patient's tumour, selects those that best recognise the cancer, grows them to large numbers and infuses them back. confirmedas of 2026-10-10

    6. [6]

      NCI identifies three obstacles for CAR T cells in solid tumours: few suitable surface antigens, an immunosuppressive tumour environment, and molecular variation between and within tumours. confirmedas of 2025-02-26

    7. [7]

      Immune checkpoints are a normal part of the immune system that stop immune responses from becoming so strong that they destroy healthy cells. confirmedas of 2026-10-10

    8. [8]

      Some tumours dampen T-cell responses by producing large amounts of the checkpoint protein PD-L1; checkpoint inhibitors block this binding so T cells can attack the cancer. confirmedas of 2026-10-10

    9. [9]

      Common side effects of checkpoint inhibitors include rash, diarrhoea and fatigue; rarer effects include widespread inflammation that can affect organs such as the lungs, colon, liver, heart and thyroid. confirmedas of 2026-10-10

    10. [10]

      The CTLA-4 pathway acts mainly at the level of lymph nodes during initial T-cell activation, while the PD-1 pathway acts mainly in tissues, where its ligands PD-L1 and PD-L2 are expressed in the tumour microenvironment. confirmedas of 2026-10-10

    11. [11]

      In an ipilimumab melanoma trial, 64% of patients had an immune-related adverse event of any grade and 18% had one of grade 3 or higher. confirmedas of 2026-10-10

    12. [12]

      NCI describes two main types of T-cell transfer therapy: tumour-infiltrating lymphocyte (TIL) therapy and CAR T-cell therapy. confirmedas of 2026-10-10

    13. [13]

      Cancer treatment vaccines treat existing cancer by strengthening the body's defences against it, unlike preventive vaccines that guard against cancer-causing agents. confirmedas of 2026-10-10

    14. [14]

      On 16 May 2024 the FDA granted accelerated approval to tarlatamab (Imdelltra), a DLL3 x CD3 bispecific T-cell engager, for extensive-stage small cell lung cancer after platinum chemotherapy; 40% of 99 patients responded. confirmedas of 2024-05-16

    15. [15]

      In a 16-patient pancreatic cancer study, the individualised mRNA vaccine autogene cevumeran induced new neoantigen-specific T cells in 8 patients, and these responders had longer recurrence-free survival than non-responders (median not reached vs 13.4 months). confirmedas of 2023-06-01

    16. [16]

      A 2019 study estimated that 43.6% of US patients with cancer were eligible for checkpoint inhibitors in 2018 but only about 12.5% would respond to them. confirmedas of 2019-05-03

    Revision history (1)
    1. Page created.

    Created Oct 10, 2026. Last reviewed by an editor on Oct 10, 2026. Next scheduled review: Jan 10, 2027.

    Cite this page

    "How the immune system fights cancer, and how tumours escape." ContentLora, updated Oct 10, 2026. https://contentlora.com/explain/how-the-immune-system-fights-cancer

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